Microbiome最新文献

Background: Rumen microbial nitrogen metabolism is crucial for animal health, productivity, and environmental sustainability in ruminants. Natural products like biochanin A are garnering interest as potential feed additives due to their beneficial effects and safety profiles. Here, we collected total mixed diet, plasma, milk, urine, and feces samples of dairy goats to evaluate the impact of biochanin A on nitrogen metabolism and elucidated regulatory mechanisms of nitrogen metabolism using multi-omics approaches by analyzing plasma metabolites and ruminal microbial communities.

Results: Supplementation with biochanin A significantly enhanced nitrogen utilization efficiency of dairy goats. Plasma metabolomics revealed that biochanin A altered pathways related to amino acid biosynthesis/metabolism and glycolysis/gluconeogenesis. In the rumen, biochanin A enriched microbial strains from the families Selenomonadaceae and Aminobacteriaceae. Up-regulated proteins predominantly associated with glycolysis were identified by metaproteomics. Integrated metagenomic and metaproteomic analyses demonstrated that biochanin A positively influenced carbohydrate metabolism, amino acid metabolism, and energy metabolism pathways.

Conclusion: Biochanin A enhances nitrogen metabolism by regulating rumen microbial community function, supporting its potential as a natural feed additive to improve nitrogen utilization of ruminants. Video Abstract.

Background: Methamphetamine (MA) abuse is a global public problem and methamphetamine addiction lacks of effective treatment. The gut microbes, involved in the gut-brain axis, remotely regulate methamphetamine addiction.

Results: In this study, we identified that Lactobacillus johnsonii (L. johnsonii) is involved in the metabolism of tyrosine. MA addiction disrupts the balance of gut microbes, reducing the abundance of L. johnsonii, destroying intestinal barrier integrity, and increasing the tyrosine level. The outbreak of tyrosine promotes a greater craving for MA in mice since it transfers from the intestine to VTA and NAc to promote microglia immune reactivity, which reduces energy supply to neurons and decreases presynaptic mitochondria in dopaminergic neurons. As a consequence, the dopaminergic presynaptic membrane reuptake process based on vesicular transport is affected, leading to maintain of dopamine in the synaptic cleft acting on the postsynaptic membrane with synaptic plasticity changes, resulting in MA craving. L. johnsonii transplantation rescues mice from MA craving by promoting the metabolism of tyrosine in intestine and improves the neuronal function in NAc and VTA.

Conclusions: Our results reveal that MA addiction disrupts gut microbiota homeostasis and promotes tyrosine-mediated dopamine system dysfunction. L. johnsonii transplantation is recommended for the treatment of methamphetamine craving.

Background: The mechanisms by which microbiota from disease-resistant populations or animals improve intestinal immune defense remain incompletely elucidated. Tibetan pig, a renowned disease-resistant breed, serve as a valuable research subject for the health of humans and economic animals.

Results: In this study, fecal microbiota transplantation from Tibetan piglets into mice conferred enhanced resistance to C. rodentium DBS100. Further microbiota profiling and metabolomics analysis showed this protection may be partly ascribed to C. butyricum SLZX19-05 in recipients' colon. Administration of C. butyricum SLZX19-05 to germ-free mice resulted in the significantly increased lysozyme expression within colonic macrophages, subsequently bolstering the resistance to C. rodentium infection. In mice and piglets, this C. butyricum similarly elevated the lysozyme level in colon and decreased diarrhea incidence. Conversely, lyz1-knockout heightened mice's susceptibility to C. rodentium, highlighting lysozyme's critical role in immune defense. Mechanistically, this study systematically revealed that C. butyricum enhanced lysozyme expression by inhibiting mTORC1-HDAC3/8 pathway, leading to the increased H4K31 Crotonylation (H4K31Cr) and openness of an upstream region of lyz1 promoter via butyrate in macrophages. Additionally, H4K31-mutant mice showed the leukopenia, further validating the significance of H4K31Cr in immune regulation.

Conclusions: Collectively, mTORC1-HDAC3/8-H4K31Cr pathway is a key mechanism by which butyrate-producing commensal bacteria enhance immune defense in gut. This discovery provides a novel foundation for the screening and application of the next generation of butyrate-producing probiotics. Video Abstract.

Background: The objective of this study was to examine the relationship between two different types of silage (saline; SQ and non-saline; NSQ) and rumen metabolism in Tibetan sheep.

Results: It was found that sheep in the saline silage (SQ group) exhibited superior apparent quality (e.g., crude protein, crude fat, DM, crude polysaccharide, polyphenols, and flavonoid), secondary metabolite profiles (e.g., Proline, Leucine, Alanine, Pyruvate), and fermentation microbial populations (e.g., Firmicutes, Bacteroidota, and Lactobacillus) compared to the non-saline (NSQ) silage group. However, the higher fiber and carbohydrate content in the SQ silage resulted in lower relative feed value (RFV) values, which was also responsible for the increased proportion of Rikenellaceae_RC9_gut_group in the rumen of the SA-1 group. The greater contents of amino acids and saccharides in the GQ silage were also responsible for the acceleration of the growth and metabolic processes of rumen microorganisms. Furthermore, the presence of phenolic compounds, glutamate, and lactic acid bacteria in the SQ silage may also have contributed to the consumption of histamine in the rumen, while the accumulation of phenolic compounds may have been responsible for the reduced contents of short-chain fatty acids in the rumen. Furthermore, a probable association between histamine decline and ATP accumulate was identified.

Conclusions: In conclusion, metabolites and microorganisms enriched in saline silage exert a positive influence on the metabolites and microorganisms in the rumen of Tibetan sheep. Additionally, the accumulation of phenolic compounds, glutamate, and lactic acid bacteria in saline-alkali land silage may lead to the decrease of histamine in the rumen of Tibetan sheep and is also the cause of the decrease in short-chain fatty acid levels in the rumen. Video Abstract.

Background: Grapevines are among the most economically important fruit crops, and the microbiome profoundly influences their health, yield, and quality. However, mechanistic insights into microbiome-orchestrated grapevine biology remain limited.

Results: Here, we conduct large-scale pan-metagenomic and pan-metatranscriptomic analyses of the phyllosphere microbiome from 107 grapevine accessions spanning 34 Vitis species. We show that the grapevine core microbiome is dominated by phyla Bacillota and Pseudomonadota. Leveraging PacBio sequencing, we assembled 19 high-quality metagenome-assembled genomes (MAGs) from the grapevine pan-microbiome, representing the first MAG reconstruction in plant-associated microbial communities using PacBio reads. These MAGs encode genes associated with antibiotic resistance, secondary metabolism, and carbohydrate-active enzymes (CAZymes), which could potentially influence grapevine biology. During downy mildew (DM) infection, DM-resistant grapevines exhibit significantly higher microbial network complexity than susceptible counterparts. Among the key taxa contributing to this complexity, Bacillota emerged as the dominant phylum, displaying strong abundance correlations with phylum Euglenozoa and Cyanobacteriota, and an isolated Bacillota species from the grapevine leaves, Bacillus cereus, demonstrated potent biocontrol activity against DM infection. Pan-metatranscriptomic analysis further revealed significant upregulation of eukaryotic microbial genes involved in primary and secondary metabolism.

Conclusions: This pan-metagenomic study offers unprecedented insights into the complex structure, diversity, and functional roles of the grapevine phyllosphere microbiome and presents valuable genomic and microbial resources for microbiome research and engineering to enhance viticulture productivity and quality. Video Abstract.

Objective: To investigate the influence of environmental factors on the composition and structure of the vaginal microbiome and to explore the interaction among environmental factors, vaginal microbiome, and outcomes of assisted reproductive technology (ART).

Methods: Adonis test was utilized to evaluate the impact of 33 host/environmental variables on vaginal microbiome. Distributed lag nonlinear model analysis (DLNM), Mfuzz analysis, and linear mixed effect model were employed to establish the correlations between ambient temperature and vaginal microbes.

Results: Ambient temperature was one of the most important environmental factors associated with vaginal microbiome. As the temperature increased, succession of vaginal microbes showed four patterns of abundance variation. Furthermore, a group of vaginal microbes showed a preference for certain temperatures, and these microbes' varying interactions partly drove the shift of microbial networks at different temperatures. The community assembly process of vaginal microbiome deviated from neutral model and exposure to ambient temperature did not affect the role of stochastic processes in shaping vaginal microbial community. Notably, vaginal microbiome prior to embryo transfer was significantly associated with preterm birth. Preterm women exhibited higher abundance of Lactobacillus iners and lower abundance of Lactobacillus crispatus.

Conclusions: Ambient temperature change can affect the structure and composition of the vaginal microbiome and correlate with the abundance of certain vaginal microbes. Temperature-sensitive vaginal bacteria may affect the risk of future preterm births. Video Abstract.

Background: The contribution of dietary interventions, particularly lysine-restricted diets (LRD), to ameliorating obesity-associated anxiety-like behaviors remains elusive, with limited evidence clarifying microbiota-metabolite-brain axis pathways involved.

Results: Herein, our results demonstrated that LRD attenuated high-fat diet (HFD)-induced anxiety-like behaviors while concomitantly reducing body weight and improving glucose metabolism. Furthermore, LRD significantly remodeled gut microbiota composition, most notably enriching the abundance of Oscillibacter. We then screened and identified that both viable and encapsulated Oscillibacter ruminantium alleviated obesity- and chronic restraint stress-induced anxiety-like behaviors, with microencapsulated formulations conferring superior anxiolytic efficacy. Notably, the obtained data revealed that LRD reversed HFD-induced the depletion of tryptophol, which was established as the metabolite of Oscillibacter ruminantium, and LRD could also alleviate the intestinal barrier impairment caused by HFD. Mechanistic results further demonstrated that tryptophol supplementation ameliorated HFD-driven anxiety-like phenotypes by inhibiting FTO-mediated reader protein IGF2BP1, and thereby reducing m⁶A modification of Lgr6 mRNA.

Conclusion: LRD attenuates obesity-associated anxiety-like behaviors by enriching Oscillibacter ruminantium and modulating tryptophol production, thereby activating the FTO-IGF2BP1-LGR6 signaling axis. These findings would indicate LRD as a microbiota-directed therapeutic strategy for neurobehavioral comorbidities of metabolic stress.

Background: Post-stroke cognitive impairment (PSCI) affects up to half of stroke survivors, severely impacting their quality of life. Despite its prevalence, the pathogenesis of PSCI remains poorly understood, and no specific pharmacological treatments are currently available.

Results: In PSCI patients, fecal butyrate levels were significantly reduced and correlated with cognitive scores. A machine learning model incorporating butyrate levels, butyrate-producing bacteria, and clinical factors (education, smoking, body mass index [BMI], hemoglobin) demonstrates strong predictive performance (area under the curve [AUC]: 0.793 internal, 0.795 external validation). In a transient middle cerebral artery occlusion (tMCAO) mouse model, both sexes displayed sustained gut microbiota dysbiosis featuring decreased butyrate-producing bacteria and fecal butyrate concentrations, concomitant with hippocampal neuronal loss and microglial activation. Sodium oligomannate (GV-971) treatment ameliorated cognitive impairment in a sex-independent manner and restored butyrate-producing gut bacteria. Metagenomic analysis revealed that GV-971 enhanced butyrate production by promoting D-glucuronate degradation and upregulating butyrate synthesis pathway abundance. The elevated butyrate promoted acetylation of histone H3 at lysines 9 and 14 (Ac-H3K9/K14) in colonic and hippocampal neurons, stimulating neurogenesis, while concurrently reducing gut-derived lipopolysaccharide (LPS) and microglial inflammation. Antibiotic treatment and fecal microbiota transplantation established the essential role of butyrate-producing microbiota in mediating GV-971's effects. In vitro, butyrate supplementation significantly inhibited HDAC3 enzymatic activity in HT22 cells and alleviated LPS-induced inflammatory responses in BV2 microglia.

Conclusions: Intestinal butyrate levels are significantly associated with PSCI. GV-971 mitigates post-stroke cognitive decline by modulating the gut microbiota to increase butyrate production, highlighting its potential as a therapeutic agent for PSCI.

Background: Nitrogen-fixing bacteria (NFBs) play a critical role in biological nitrogen fixation for supplying essential nitrogen nutrients to plants in agriculture and natural ecosystems. Especially, these bacteria and Leguminosae plants form symbiosis to improve plant growth and soil fertility. Theoretically, the inoculation of NFBs into soils increases biological nitrogen fixation, but the efficiency of NFBs is frequently compromised by the low capacity of NFB root colonization. In this study, we introduced the synthetic bacterium EcCMC, which was genetically engineered to express the surface-displayed artificial polysaccharide (PS)-recognizing protein Cmc, to test if it can improve NFBs root colonization in representative Leguminosae plants, including Astragalus sinicus and Medicago sativa. Rhizosphere microbiomes, biochemical indicators, and plant yields were evaluated after 28 days in the three treatments, i.e., the control group without addition of any exogenous bacterium, the NFBs plus EcM (bacteria only expressing mCherry rather than Cmc) group, and the NFBs plus EcCMC group (n = 3).

Results: Owing to its polysaccharide-binding capacity, EcCMC strongly bound to the surface of A. sinicus roots. This binding was followed by the increased recruitment of the exogenous NFBs, Sinorhizobium meliloti and Sphingomonas endophytica, on the roots. As revealed by amplicon sequencing of the 16S rRNA gene, a combined inoculation of EcCMC and the NFBs increased the relative abundance of both Rhizobiales and Sphingomonadales, two important bacterial groups involved in nitrogen fixation. Consistently, metabolomic analysis showed that the metabolites involved in nitrogen fixation remarkably accumulated in the rhizosphere soils inoculated with NFBs plus EcCMC. Moreover, inoculation of NFBs plus EcCMC increased the activity of nitrogenase from 10.8 ~ 11.3 to 16.2 nmol/min/g (significant difference, p < 0.05, t-test), together with the total soil nitrogen levels from 217 ~ 258 to 414 mg/kg (significant difference, p < 0.05), and the soil organic matter levels from 19.5 ~ 20.8 to 23.6 mg/kg (significant difference, p < 0.05). Consequently, the yield of A. sinicus was remarkably improved by the inoculation of NFBs plus EcCMC. Similar results were observed in the experiments using Medicago sativa.

Conclusions: This study sheds a novel light on a synthetic biology-assisted regulation of rhizosphere microbiomes for enhanced nitrogen fixation and soil fertility in Leguminous plants. The designed polysaccharide-binding protein may be used as a universal tool to promote plant growth and enhance crop resilience in the future. Video Abstract.

Background: Host plant significantly influences herbivorous insect fitness, while plant-mediated gut microbiota are recognized as a key determinant of insect performance. However, to what extent the differential performance of herbivorous insects on various plants is attributed to plant properties versus plant-mediated gut microbiota remains less clear.

Results: Here, we initially observed that the leaf beetle Plagiodera versicolora preferred and exhibited superior performance on Salix babylonica compared with three other host plants. Intriguingly, eliminating larval gut microbiota abolished this preference-performance relationship, resulting in the loss of superior performance on S. babylonica. Further analysis of the larval gut microbiota revealed that Rosenbergiella nectarea was significantly enriched in S. babylonica-fed larvae and positively correlated with larval performance. Reintroduction of R. nectarea, but not two other gut commensal bacteria, restored the superior performance of germ-free (GF) larvae fed S. babylonica. Transcriptomic analysis linked this growth promotion to enhanced nutritional metabolism and developmental signaling. Integrated metabolomic and transcriptomic analyses further identified eight candidate genes underlying the observed effects. Notably, knockdown of either PvABCG1 or PvABCG5 recapitulated the microbiota-depleted phenotype, whereas reintroduction of R. nectarea into GF larvae only fully rescued PvABCG5 knockdown-induced growth retardation. Concurrently, R. nectarea supplementation increased the expression of key 20E synthesis genes (PvSPO, PvPHM, PvSHD), suggesting promotion of larval development may occur via a PvABCG5-mediated cholesterol-to-20E synthesis pathway.

Conclusions: Collectively, our results suggest that host plant-induced differential performance in herbivorous insects largely depends on their gut microbiota, suggesting a crucial role of the gut microbiome in herbivore host preference and the "preference-performance" relationship. Video Abstract.