Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 152
Filter
2.
Nat Commun ; 15(1): 3154, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38605043

ABSTRACT

Forest carbon sequestration capacity in China remains uncertain due to underrepresented tree demographic dynamics and overlooked of harvest impacts. In this study, we employ a process-based biogeochemical model to make projections by using national forest inventories, covering approximately 415,000 permanent plots, revealing an expansion in biomass carbon stock by 13.6 ± 1.5 Pg C from 2020 to 2100, with additional sink through augmentation of wood product pool (0.6-2.0 Pg C) and spatiotemporal optimization of forest management (2.3 ± 0.03 Pg C). We find that statistical model might cause large bias in long-term projection due to underrepresentation or neglect of wood harvest and forest demographic changes. Remarkably, disregarding the repercussions of harvesting on forest age can result in a premature shift in the timing of the carbon sink peak by 1-3 decades. Our findings emphasize the pressing necessity for the swift implementation of optimal forest management strategies for carbon sequestration enhancement.


Subject(s)
Carbon Sequestration , Forests , Trees , China , Biomass , Carbon/analysis
3.
J Hazard Mater ; 470: 134156, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38565015

ABSTRACT

While antimony (Sb) and arsenic (As) co-contamination in subsurface soil systems due to the legacy of Sb smelting wastes has been documented, the role of inherent heterogeneity on pollutant migration is largely overlooked. Herein this study investigated Sb and As migration in a slag impacted, vertically stratified subsurface at an abandoned Sb smelter. A 2-dimensional flume was assembled as a lab-scale analogue of the site and subject to rainfall and stop-rain events. Reactive transport modeling was then performed by matching the experimental observations to verify the key factors and processes controlling pollutant migration. Results showed that rainfall caused Sb and As release from the shallow slag layer and promoted their downward movement. Nevertheless, the less permeable deeper layers limited physical flow and transport, which led to Sb and As accumulation at the interface. The re-adsorption of Sb and As onto iron oxides in the deeper, more acidic layers further retarded their migration. Because of the large difference between Sb and As concentrations, Sb re-adsorption was much less effective, which led to higher mobility. Our findings overall highlight the necessity of understanding the degree and impacts of physicochemical heterogeneity for risk exposure assessment and remediation of abandoned Sb smelting sites.

4.
Sci Bull (Beijing) ; 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38553345

ABSTRACT

Lunar materials are overall more reducing compared with their terrestrial counterparts, but the mechanism remains to be elucidated. In this study, we present a possible explanation for the changes in redox state of the lunar regolith caused by impact events, based on our investigations of the impact glass beads from Chang'e-5 mission. These glass beads contain iron metal grains and show concentration gradients of FeO and K2O (with or without Na2O) from their rims to centers. The compositional profiles exhibit error-function-like shapes, which indicates a diffusion-limited mechanism. Our numerical modeling results suggest that the iron metal grains on the surface of the glass beads were generated through the reduction of FeO by elemental K and (or) Na produced during the impact events. Meanwhile, the iron metal grains inside the bead may have formed due to oxygen diffusion driven by redox potential gradients. Furthermore, our study suggests that impact processes intensify the local reducing conditions, as evidenced by the presence of calcium sulfide particles within troilite grains that coexist with iron metal grains on the surface of the glass beads. This study provides insights into the oxygen diffusion kinetics during the formation of iron metal spherules and sheds light on the changes in redox conditions of lunar materials caused by impact events.

5.
Proc Natl Acad Sci U S A ; 121(13): e2313334121, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38498717

ABSTRACT

Multiple facets of global change affect the earth system interactively, with complex consequences for ecosystem functioning and stability. Simultaneous climate and biodiversity change are of particular concern, because biodiversity may contribute to ecosystem resistance and resilience and may mitigate climate change impacts. Yet, the extent and generality of how climate and biodiversity change interact remain insufficiently understood, especially for the decomposition of organic matter, a major determinant of the biosphere-atmosphere carbon feedbacks. With an inter-biome field experiment using large rainfall exclusion facilities, we tested how drought, a common prediction of climate change models for many parts of the world, and biodiversity in the decomposer system drive decomposition in forest ecosystems interactively. Decomposing leaf litter lost less carbon (C) and especially nitrogen (N) in five different forest biomes following partial rainfall exclusion compared to conditions without rainfall exclusion. An increasing complexity of the decomposer community alleviated drought effects, with full compensation when large-bodied invertebrates were present. Leaf litter mixing increased diversity effects, with increasing litter species richness, which contributed to counteracting drought effects on C and N loss, although to a much smaller degree than decomposer community complexity. Our results show at a relevant spatial scale covering distinct climate zones that both, the diversity of decomposer communities and plant litter in forest floors have a strong potential to mitigate drought effects on C and N dynamics during decomposition. Preserving biodiversity at multiple trophic levels contributes to ecosystem resistance and appears critical to maintain ecosystem processes under ongoing climate change.


Subject(s)
Droughts , Ecosystem , Biodiversity , Forests , Plant Leaves , Carbon
7.
Nanoscale ; 16(7): 3324-3346, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38276956

ABSTRACT

Infectious diseases caused by bacterial invasions have imposed a significant global health and economic burden. More worryingly, multidrug-resistant (MDR) pathogenic bacteria born under the abuse of antibiotics have further escalated the status quo. Nowadays, at the crossroads of multiple disciplines such as chemistry, nanoscience and biomedicine, nanozymes, as enzyme-mimicking nanomaterials, not only possess excellent bactericidal ability but also reduce the possibility of inducing resistance. Thus, nanozymes are promising to serve as an alternative to traditional antibiotics. Nanozymes that mimic peroxidase (POD) activity are also known as POD nanozymes. In recent years, POD nanozymes have become one of the most frequently reported and effective nanozymes due to their broad-spectrum bactericidal properties and unique sterilization mechanism. In this review, we introduce the mechanism as well as the classification of POD nanozymes. More importantly, to further improve the antibacterial efficacy of POD nanozymes, we elaborate on three aspects: (1) improving the physicochemical properties; (2) regulating the catalytic microenvironment; and (3) designing multimodel POD nanozymes. In addition, we review the nanosafety of POD nanozymes for discussing their potential toxicity. Finally, the remaining challenges of POD nanozymes and possible future directions are discussed. This work provides a systematic summary of POD nanozymes and hopefully contributes to the early clinical translation.


Subject(s)
Nanostructures , Peroxidase , Humans , Peroxidases , Anti-Bacterial Agents/pharmacology , Catalysis , Coloring Agents
8.
J Med Virol ; 96(1): e29380, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38235849

ABSTRACT

Hepatic venous pressure gradient (HVPG) is the gold standard for evaluating clinically significant portal hypertension (CSPH). However, reliable noninvasive methods are limited. Our study aims to investigate the diagnostic value of serum Golgi protein 73 (GP73) for CSPH in patients with compensated cirrhosis. The study enrolled 262 consecutive patients with compensated cirrhosis from three centers in China from February 2021 to September 2023, who underwent both serum GP73 tests and HVPG measurements. CSPH was defined as HVPG ≥ 10 mmHg. Diagnostic accuracy was evaluated using the areas under the receiver operating characteristic curve (AUC). The prevalence of CSPH was 56.9% (n = 149). There were significant differences between the CSPH and non-CSPH groups in the median serum GP73 level (126.8 vs. 73.1 ng/mL, p < 0.001). GP73 level showed a significant positive linear correlation with HVPG (r = 0.459, p < 0.001). The AUC for the diagnosis of CSPH using serum GP73 alone was 0.75 (95% confidence interval [CI] 0.68-0.81). Multivariate logistic regression analysis determined that the levels of GP73, platelets and international normalized ratio were independently associated with CSPH. The combination of these three markers was termed "IP73" score with an AUC value of 0.85 (95% CI 0.80-0.89) for CSPH. Using 0 as a cut-off value, the specificity and sensitivity of IP73 score were 77.9% and 81.9%, respectively. The IP73 score offers a novel, simple and noninvasive method of assessing CSPH in patients with compensated cirrhosis. A cut-off value of the IP73 score at 0 can distinguish patients with or without CSPH.


Subject(s)
Elasticity Imaging Techniques , Hypertension, Portal , Humans , Biomarkers , Hypertension, Portal/complications , Hypertension, Portal/diagnosis , Liver , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , ROC Curve , Time Factors
9.
Mol Ecol ; 33(4): e17241, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38078555

ABSTRACT

Across ecology, and particularly within microbial ecology, there is limited understanding how the generation and maintenance of diversity. Although recent work has shown that both local assembly processes and species pools are important in structuring microbial communities, the relative contributions of these mechanisms remain an important question. Moreover, the roles of local assembly processes and species pools are drastically different when explicitly considering the potential for saturation or unsaturation, yet this issue is rarely addressed. Thus, we established a conceptual model that incorporated saturation theory into the microbiological domain to advance the understanding of mechanisms controlling soil bacterial diversity during forest secondary succession. Conceptual model hypotheses were tested by coupling soil bacterial diversity, local assembly processes and species pools using six different forest successional chronosequences distributed across multiple climate zones. Consistent with the unsaturated case proposed in our conceptual framework, we found that species pool consistently affected α-diversity, even while local assembly processes on local richness operate. In contrast, the effects of species pool on ß-diversity disappeared once local assembly processes were taken into account, and changes in environmental conditions during secondary succession led to shifts in ß-diversity through mediation of the strength of heterogeneous selection. Overall, this study represents one of the first to demonstrate that most local bacterial communities might be unsaturated, where the effect of species pool on α-diversity is robust to the consideration of multiple environmental influences, but ß-diversity is constrained by environmental selection.


Subject(s)
Biodiversity , Microbiota , Forests , Ecology , Bacteria/genetics , Soil , Ecosystem
10.
Blood ; 143(7): 582-591, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-37971194

ABSTRACT

ABSTRACT: Concurrent Bruton tyrosine kinase and BCL2 inhibition has not yet been investigated in Waldenström macroglobulinemia (WM). We performed an investigator-initiated trial of ibrutinib and venetoclax in symptomatic treatment-naïve patients with MYD88-mutated WM. Patients received ibrutinib 420 mg once daily (cycle 1), followed by a ramp-up of venetoclax to 400 mg daily (cycle 2). The combination was then administered for 22 additional 4-week cycles. The attainment of very good partial response (VGPR) was the primary end point. Forty-five patients were enrolled in this study. The median baseline characteristics were as follows: age 67 years, serum IgM 43 g/L, and hemoglobin 102 g/L. Seventeen patients (38%) carried CXCR4 mutations. Nineteen patients (42%) achieved VGPR. Grade 3 or higher adverse events included neutropenia (38%), mucositis (9%), and tumor lysis syndrome (7%). Atrial fibrillation occurred in 3 (9%), and ventricular arrhythmia in 4 (9%) patients that included 2 grade 5 events. With a median follow-up of 24.4 months, the 24-month progression-free survival (PFS) and overall survival (OS) rates were 76% and 96%, respectively, and were not impacted by CXCR4 mutations. The median time on therapy was 10.2 months, and the median time after the end of therapy (EOT) was 13.3 months. Eleven of the 12 progression events occurred after EOT, and the 12-month PFS rates after EOT were 79%; 93% if VGPR was attained, and 69% for other patients (P = .12). Ibrutinib and venetoclax induced high VGPR rates and durable responses after EOT, although they were associated with a higher-than-expected rate of ventricular arrhythmia in patients with WM, leading to early study treatment termination. This trial was registered at www.clinicaltrials.gov as #NCT04273139.


Subject(s)
Adenine/analogs & derivatives , Bridged Bicyclo Compounds, Heterocyclic , Sulfonamides , Waldenstrom Macroglobulinemia , Humans , Aged , Waldenstrom Macroglobulinemia/drug therapy , Waldenstrom Macroglobulinemia/genetics , Piperidines , Arrhythmias, Cardiac
11.
Nat Commun ; 14(1): 4920, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37582962

ABSTRACT

Metallized arrays of three-dimensional (3D) nanoarchitectures offer new and exciting prospects in nanophotonics and nanoelectronics. Engineering these repeating nanoarchitectures, which have dimensions smaller than the wavelength of the light source, enables in-depth investigation of unprecedented light-matter interactions. Conventional metal nanomanufacturing relies largely on lithographic methods that are limited regarding the choice of materials and machine write time and are restricted to flat patterns and rigid structures. Herein, we present a 3D nanoprinter devised to fabricate flexible arrays of 3D metallic nanoarchitectures over areas up to 4 × 4 mm2 within 20 min. By suitably adjusting the electric and flow fields, metal lines as narrow as 14 nm were printed. We also demonstrate the key ability to print a wide variety of materials ranging from single metals, alloys to multimaterials. In addition, the optical properties of the as-printed 3D nanoarchitectures can be tailored by varying the material, geometry, feature size, and periodic arrangement. The custom-designed and custom-built 3D nanoprinter not only combines metal 3D printing with nanoscale precision but also decouples the materials from the printing process, thereby yielding opportunities to advance future nanophotonics and semiconductor devices.

12.
Mol Cell Biochem ; 2023 Jul 12.
Article in English | MEDLINE | ID: mdl-37436653

ABSTRACT

Inflammatory bone disease is a general term for a series of diseases caused by chronic inflammation, which leads to the destruction of bone homeostasis, that is, the osteolytic activity of osteoclasts increases, and the osteogenic activity of osteoblasts decreases, leading to osteolysis. Macrophages are innate immune cell with plasticity, and their polarization is related to inflammatory bone diseases. The dynamic balance of macrophages between the M1 phenotype and the M2 phenotype affects the occurrence and development of diseases. In recent years, an increasing number of studies have shown that extracellular vesicles existing in the extracellular environment can act on macrophages, affecting the progress of inflammatory diseases. This process is realized by influencing the physiological activity or functional activity of macrophages, inducing macrophages to secrete cytokines, and playing an anti-inflammatory or pro-inflammatory role. In addition, by modifying and editing extracellular vesicles, the potential of targeting macrophages can be used to provide new ideas for developing new drug carriers for inflammatory bone diseases.

13.
Sci Total Environ ; 884: 163792, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37127160

ABSTRACT

Afforestation and reforestation (A&R) are nature-based and cost-effective solutions for enhancing terrestrial carbon sinks and facilitating faster carbon neutrality. However, the lack of hierarchical spatial-temporal maps for the carbon sequestration rate (CSR) from A&R at the national scale impedes the scientific implementation of forest management planning to a large extent. Here, we assessed the spatial-temporal CSR per area for A&R at the provincial, prefectural, and county levels in China using a forest carbon sequestration model under three climate scenarios. Results showed that the CSR of vegetation (CSRVeg), soil (CSRSoil), and the ecosystem (CSREco) significantly varied across space and time. In China, the CSRVeg, CSRSoil, and CSREco were primarily regulated by the spatial variations in temperature and precipitation. Additionally, CSRVeg was found to be positively influenced by precipitation and temperature, whereas temperature had a negative influence on CSRSoil. Therefore, the differences between the CSRVeg and CSRSoil should be emphasized in the future. These information on the spatiotemporal variation of CSR of A&R (vegetation, soil, and ecosystem) on unit area basis and at levels of province, prefecture, and county in China, can be used as a comparable protocol to estimate the carbon sinks of A&R at different scales. Overall, these hierarchical spatiotemporal maps for CSR on A&R may help to identify priority areas of forest management planning and carbon trade policy to achieve faster carbon neutrality for China in the future.


Subject(s)
Carbon Sequestration , Ecosystem , Carbon/analysis , Forests , China , Soil
14.
Glob Chang Biol ; 29(10): 2852-2864, 2023 05.
Article in English | MEDLINE | ID: mdl-36840370

ABSTRACT

Higher tree species richness generally increases the storage of soil organic carbon (SOC). However, less attention is paid to the influence of varied tree species composition on SOC storage. Recently, the perspectives for the stronger persistence of SOC caused by the higher molecular diversity of organic compounds were proposed. Therefore, the influences of tree species richness and composition on the molecular diversity of SOC need to be explored. In this study, an index of the evenness of diverse SOC chemical components was proposed to represent the potential resistance of SOC to decomposition under disturbances. Six natural forest types were selected encompassing a diversity gradient, ranging from cold temperate to tropical forests. We examined the correlations of tree species richness, composition, and functional diversity, with the evenness of SOC chemical components at a molecular level by 13 C nuclear magnetic resonance. Across the range, tree species richness correlated to the evenness of SOC chemical components through tree species composition. The negative correlation of evenness of SOC chemical components with tree species composition, and the positive correlation of evenness of SOC chemical components with tree functional diversity were found. These indicate the larger difference in tree species composition and the lower community functional diversity resulted in the higher heterogeneity of SOC chemical components among the communities. The positive correlation of the evenness of SOC chemical components with the important value of indicator tree species, further revealed the specific tree species contributing to the higher evenness of SOC chemical components in each forest type. Soil fungal and bacterial α-diversity had effect on the evenness of SOC chemical components. These findings suggest that the indicator tree species conservation might be preferrable to simply increasing tree species richness, for enhancing the potential resistance of SOC to decomposition.


Subject(s)
Ecosystem , Trees , Carbon/analysis , Soil/chemistry , Biodiversity , Forests , China
15.
Microbiome ; 11(1): 32, 2023 02 23.
Article in English | MEDLINE | ID: mdl-36814316

ABSTRACT

BACKGROUND: Gamma-delta (γδ) T cells are a major cell population in the intestinal mucosa and are key mediators of mucosal tolerance and microbiota composition. Little is known about the mechanisms by which intestinal γδ T cells interact with the gut microbiota to maintain tolerance. RESULTS: We found that antibiotic treatment impaired oral tolerance and depleted intestinal γδ T cells, suggesting that the gut microbiota is necessary to maintain γδ T cells. We also found that mice deficient for γδ T cells (γδ-/-) had an altered microbiota composition that led to small intestine (SI) immune dysregulation and impaired tolerance. Accordingly, colonizing WT mice with γδ-/- microbiota resulted in SI immune dysregulation and loss of tolerance whereas colonizing γδ-/- mice with WT microbiota normalized mucosal immune responses and restored mucosal tolerance. Moreover, we found that SI γδ T cells shaped the gut microbiota and regulated intestinal homeostasis by secreting the fecal micro-RNA let-7f. Importantly, oral administration of let-7f to γδ-/- mice rescued mucosal tolerance by promoting the growth of the γδ-/--microbiota-depleted microbe Ruminococcus gnavus. CONCLUSIONS: Taken together, we demonstrate that γδ T cell-selected microbiota is necessary and sufficient to promote mucosal tolerance, is mediated in part by γδ T cell secretion of fecal micro-RNAs, and is mechanistically linked to restoration of mucosal immune responses. Video Abstract.


Subject(s)
MicroRNAs , Microbiota , Mice , Animals , T-Lymphocytes , Receptors, Antigen, T-Cell, gamma-delta/genetics , Intestines , Intestinal Mucosa , Immunity, Mucosal
16.
Sci Total Environ ; 857(Pt 1): 159363, 2023 Jan 20.
Article in English | MEDLINE | ID: mdl-36240914

ABSTRACT

Canopy conductance (gc) is an important biophysical parameter closely related to ecosystem energy partitioning and carbon sequestration, which can be used to judge drought effect on forest ecosystems. It is very important to explore how soil moisture change affects the environmental control mechanism of gc, especially in natural oak forests in Central China where frequent extreme precipitation (P) and drought will occur in a context of climate change. In this study, variations of gc and its environmental control mechanisms in a warm-temperate forest over three consecutive years under different hydroclimatic conditions were examined by using eddy-covariance technique. Results showed that the averaged gc in the three growing seasons were 11.2, 11.3 and 7.8 mms-1, respectively, with a CV of 19.7 %. The lowest gc occurred in the year with the lowest P. Using three years of data, we found that vapor pressure deficit (VPD) exhibited the dominate effect on gc, both diffuse photosynthetically active radiation (PARdif) and air temperature (Ta) were positively correlated with gc. When relative extractable water content (REW) was larger than 0.4, however, inhibiting effect of high VPD on gc disappeared and the effect of direct photosynthetically active radiation (PARdir) on gc was larger compared to PARdif. When REW was <0.1, the positive relationship between Ta and gc became negative. Our results indicated that soil moisture ultimately shapes the environmental control mechanism of gc in a natural oak forest.


Subject(s)
Ecosystem , Quercus , Soil , Forests , Climate Change , Seasons , Water
17.
Anim Biotechnol ; 34(3): 574-584, 2023 Jun.
Article in English | MEDLINE | ID: mdl-34629027

ABSTRACT

DNA methyltransferase 2 (DNMT2) was renamed as tRNA aspartic acid methyltransferase 1 (TRDMT1) by catalyzing the methylation of tRNAAsp anti-codon loop C38. The development of sequencing of nucleic acids and protein detection techniques have prompted the demonstration that TRDMT1 mediated tRNA modification affects protein synthesis efficiency. This process affects the growth and development of animals. The DNA of 224 Qinchuan cattles aged 2-4 years old was collected in this experiment. The genetic variations of TRDMT1 exon and some intron regions were detected by mixed pool sequencing technology. qRT-PCR and Western Blot were used to detect the expression levels of mRNA and protein produced with the combination of different genetic variant loci. Three haplotypes were detected and the distribution ratios were different. Muscle tissue mRNA and protein testing showed that there were differences in mRNA expression levels among different genotypes (P < 0.05) and the protein expression levels between different genotypes show the same trend as mRNA. This study provides potential molecular materials for the improvement of Qinchuan cattle reproductivity and provides theoretical support for studying the effects of livestock TRDMT1 on animal growth and development.


Subject(s)
Body Weights and Measures , Polymorphism, Single Nucleotide , Cattle/genetics , Animals , Genotype , Haplotypes , RNA, Messenger/genetics , RNA, Messenger/metabolism
18.
Trends Plant Sci ; 28(1): 43-53, 2023 01.
Article in English | MEDLINE | ID: mdl-36115777

ABSTRACT

With the rapid accumulation of plant trait data, major opportunities have arisen for the integration of these data into predicting ecosystem primary productivity across a range of spatial extents. Traditionally, traits have been used to explain physiological productivity at cell, organ, or plant scales, but scaling up to the ecosystem scale has remained challenging. Here, we show the need to combine measures of community-level traits and environmental factors to predict ecosystem productivity at landscape or biogeographic scales. We show how theory can extend the production ecology equation to enormous potential for integrating traits into ecological models that estimate productivity-related ecosystem functions across ecological scales and to anticipate the response of terrestrial ecosystems to global change.


Subject(s)
Ecosystem , Plants , Plants/genetics , Models, Theoretical , Phenotype
19.
Front Plant Sci ; 13: 926535, 2022.
Article in English | MEDLINE | ID: mdl-36237513

ABSTRACT

Considerable evidences highlight the occurrence of increasing widespread tree mortality as a result of global climate change-associated droughts. However, knowledge about the mechanisms underlying divergent strategies of various tree species to adapt to drought has remained remarkably insufficient. Leaf stomatal regulation and embolism resistance of stem xylem serves as two important strategies for tree species to prevent hydraulic failure and carbon starvation, as comprising interconnected physiological mechanisms underlying drought-induced tree mortality. Hence, the physiological and anatomical determinants of leaf stomatal regulation and stems xylem embolism resistance are evaluated and discussed. In addition, root properties related to drought tolerance are also reviewed. Species with greater investment in leaves and stems tend to maintain stomatal opening and resist stem embolism under drought conditions. The coordination between stomatal regulation and stem embolism resistance are summarized and discussed. Previous studies showed that hydraulic safety margin (HSM, the difference between minimum water potential and that causing xylem dysfunction) is a significant predictor of tree species mortality under drought conditions. Compared with HSM, stomatal safety margin (the difference between water potential at stomatal closure and that causing xylem dysfunction) more directly merge stomatal regulation strategies with xylem hydraulic strategies, illustrating a comprehensive framework to characterize plant response to drought. A combination of plant traits reflecting species' response and adaptation to drought should be established in the future, and we propose four specific urgent issues as future research priorities.

20.
Microbiome ; 10(1): 174, 2022 10 17.
Article in English | MEDLINE | ID: mdl-36253847

ABSTRACT

BACKGROUND: The gut microbiome plays an important role in autoimmunity including multiple sclerosis and its mouse model called experimental autoimmune encephalomyelitis (EAE). Prior studies have demonstrated that the multiple sclerosis gut microbiota can contribute to disease, hence making it a potential therapeutic target. In addition, antibiotic treatment has been shown to ameliorate disease in the EAE mouse model of multiple sclerosis. Yet, to this date, the mechanisms mediating these antibiotic effects are not understood. Furthermore, there is no consensus on the gut-derived bacterial strains that drive neuroinflammation in multiple sclerosis. RESULTS: Here, we characterized the gut microbiome of untreated and vancomycin-treated EAE mice over time to identify bacteria with neuroimmunomodulatory potential. We observed alterations in the gut microbiota composition following EAE induction. We found that vancomycin treatment ameliorates EAE, and that this protective effect is mediated via the microbiota. Notably, we observed increased abundance of bacteria known to be strong inducers of regulatory T cells, including members of Clostridium clusters XIVa and XVIII in vancomycin-treated mice during the presymptomatic phase of EAE, as well as at disease peak. We identified 50 bacterial taxa that correlate with EAE severity. Interestingly, several of these taxa exist in the human gut, and some of them have been implicated in multiple sclerosis including Anaerotruncus colihominis, a butyrate producer, which had a positive correlation with disease severity. We found that Anaerotruncus colihominis ameliorates EAE, and this is associated with induction of RORγt+ regulatory T cells in the mesenteric lymph nodes. CONCLUSIONS: We identified vancomycin as a potent modulator of the gut-brain axis by promoting the proliferation of bacterial species that induce regulatory T cells. In addition, our findings reveal 50 gut commensals as regulator of the gut-brain axis that can be used to further characterize pathogenic and beneficial host-microbiota interactions in multiple sclerosis patients. Our findings suggest that elevated Anaerotruncus colihominis in multiple sclerosis patients may represent a protective mechanism associated with recovery from the disease. Video Abstract.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Gastrointestinal Microbiome , Multiple Sclerosis , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteria/genetics , Butyrates , Clostridiales , Disease Models, Animal , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Humans , Mice , Mice, Inbred C57BL , Multiple Sclerosis/drug therapy , Multiple Sclerosis/microbiology , Neuroinflammatory Diseases , Nuclear Receptor Subfamily 1, Group F, Member 3 , Vancomycin/therapeutic use
SELECTION OF CITATIONS
SEARCH DETAIL
...