Microbiome最新文献

Background: Habitat fragmentation and degradation have led to the critical endangerment of numerous wild plant species. Although significant achievements in the conservation of endangered wild plants in various regions worldwide, the interaction mechanisms between these plants and their associated rhizosphere microorganisms have yet to be fully elucidated.

Results: Here, we present a communication model between the endangered wild plant Qingdao lily (Lilium tsingtauense) and its associated rhizosphere microorganisms. We isolated a rhizosphere fungus, Trichoderma longibrachiatum QDAU 0920, which effectively colonizes the roots of Qingdao lily and significantly promotes root growth. This growth enhancement is mediated by multiple plant hormones, with auxin playing a particularly prominent role. Further investigation revealed that a non-canonical AUX/IAA protein of the LtIAA16 may augment the transcriptional activation activity of LtARF22 by competitively interacting with LtIAA6, LtIAA17, and LtIAA11, thereby facilitating root growth in Qingdao lily. The growth-promoting effects of this interaction were subsequently validated in several other plant species, including tomato, pepper, corn, pumpkin, and cucumber. Notably, T. longibrachiatum QDAU 0920 forms synthetic microbial consortia (SynComs) in conjunction with other Trichoderma and Penicillium species. These SynComs consistently enhance the growth of Qingdao lily as well as other lily species such as L. lancifolium, Lilium 'Avalon Sunset', and Lilium 'Deliana'.

Conclusion: Collectively, these findings underscore the considerable potential of native microorganisms in the development of plant growth-promoting agents and the conservation of endangered plant species. Video Abstract.

Background: The ocular surface microbiome (OSM) in patients with meibomian gland dysfunction (MGD) differs from that of healthy individuals. However, the precise role of OSM in MGD remains unknown. Therefore, we aimed to investigate the mechanism of OSM in the inflammation of MGD and the effects of topical sodium butyrate (SB) treatment in ApoE^-/- mice.

Methods: ApoE^-/- (n = 36) and wild-type C57BL/6J (n = 16) mice served as MGD models and healthy controls, respectively. MGD mice were treated with safety-confirmed concentrations of SB (1, 5, and 10 mM) and PBS for 3 weeks. OSM was analyzed by 16S rRNA gene sequencing (V3-V4). The slit-lamp biomicroscopy, tear cytokines, histopathology (oil red O/PAS/TUNEL staining), and TLR4/MyD88/NF-κB signaling (RT-qPCR, immunohistochemistry, and Western blotting) were evaluated.

Results: Five-month-old ApoE^-/- mice exhibited typical clinical and histological features of MGD. These mice exhibited elevated tear levels of inflammatory cytokines and activation of the TLR4/NF-κB signaling pathway in the MGs and conjunctivae. Treatment with SB improved the corneal fluorescein staining score of MGD. The ApoE^-/- mice demonstrated dysbiosis of OSM, characterized by an increase in Proteobacteria and a decrease in Bacteroidota. Additionally, the relative abundance of Muribacter and Muribacter muris increased in ApoE^-/- mice, while that of Staphylococcus and Staphylococcus lentus decreased, and these alterations were restored by SB treatment. SB also reduced the expression of the TLR4/NF-κB p65 signaling pathway, inflammatory cytokines, and apoptosis in MGs and conjunctival tissues.

Conclusion: ApoE^-/- mice exhibited characteristic features of MGD, accompanied by dysbiosis of OSM. Topical administration of SB modulated the OSM and reduced MGD-associated inflammation. Video Abstract.

Background: The prevalence of calcium oxalate (CaOx) kidney stones is increasing, yet the underlying mechanisms remain incompletely understood. Emerging evidence suggests that gut microbiota-particularly short-chain fatty acid (SCFA)-producing bacteria-may modulate host metabolism and inflammation, thereby influencing stone formation. However, the mechanistic links between gut dysbiosis, metabolic disturbances, and CaOx stone pathophysiology remain to be fully elucidated. This study investigates gut microbiota composition, SCFA levels, and metabolomic alterations in CaOx stone formers (CSF), aiming to uncover potential pathophysiological mechanisms and therapeutic targets.

Results: Among 59 CSF and 60 healthy controls (HC), CSF exhibited significantly reduced microbial richness, with marked depletion of SCFA-producing bacteria such as Faecalibacterium prausnitzii and Eubacterium rectale. This dysbiosis was associated with decreased fecal and plasma SCFA levels, reduced 24-h urinary citrate, and widespread metabolic disturbances, particularly in tryptophan metabolism and the citrate cycle. Plasma SCFA levels were positively correlated with urinary citrate excretion, suggesting a regulatory link within the gut-kidney axis. Mendelian randomization analysis suggested that Bacteroides thetaiotaomicron may be a potential microbial risk factor for stone formation (OR = 1.26, 95% CI: 1.03-1.54, p = 0.028). In a hyperoxaluria rat model, interventions with F. prausnitzii, E. rectale, or sodium butyrate reduced renal CaOx crystal deposition and kidney injury.

Conclusions: Our findings highlight the central role of SCFA-producing bacteria and their metabolites in maintaining metabolic balance and protecting against CaOx stone formation. Gut dysbiosis and reduced SCFA levels appear to drive metabolic changes that contribute to stone development. B. thetaiotaomicron may increase stone risk, while F. prausnitzii, E. rectale, and sodium butyrate show therapeutic potential. These insights support further exploration of microbiome-based strategies for the prevention and personalized management of kidney stones. Video Abstract.

Background: Although the roles of rumen microbiome in milk yield and milk protein synthesis have been widely recognized, knowledge on how ruminal microbiome dynamic changes affect these two traits during the whole lactation is lacking. Phages have been shown to affect the microbiota, but little is known about the shift patterns of ruminal phages and if they may modulate rumen microbiome during lactation. Herein, a longitudinal study was performed to identify the potential roles of ruminal phageome and bacteriome interactions, and metabolic function shift in affecting milk yield and protein content using metagenomic and metabolomic profiling of rumen microbiome from the peak, early, and later mid-lactation stages.

Results: A total of 780 ruminal bacterial phages were identified, which exhibited two primary shifting patterns: (1) decreasing then increasing; (2) decreasing then stabilizing through the lactation. Bacteriome also showed first increasing then stabilizing or continuously declining besides exhibiting two similar shifting patterns to those of phages. By associating the differentially abundant phages with their host bacteria, we observed that significantly increased Lactococcus phage BM13, Corynebacterium phage P1201, and Campylobacter phage CJIE4-5 in peak lactation, along with Lactobacillus phage Lv-1 in early and later mid-lactation, were positively correlated with the relative abundance of their hosts. However, significantly increased Bacillus phage BCU4 and the Enterococcus phage phiNASRA1 in early mid-lactation were negatively related to their host abundance. In terms of bacteria, Ruminococcus flavefaciens and Faecalibacterium sp. CAG 74 had the highest abundance in peak lactation, whereas most Prevotella species were more abundant in early and later mid-lactation. Notably, ruminal carbohydrate and amino acid metabolism functions were enhanced in early mid-lactation. Further structural equation model and network analysis revealed that abundant Bacillus phage BCU4 and Enterococcus phage phiNASRA1 in early mid-lactation were associated with increased relative abundance of Prevotella species, possibly due to a reduction in Bacillus cereus and Enterococcus faecalis. Additionally, these Prevotella species exhibited positive relationships with rumen metabolites, such as L-phenylalanine, phenylacetylglycine, N-acetyl-D-phenylalanine, and propionate content, which contributed to the improved milk protein yield.

Conclusions: This study revealed the bacteriome and phageome interactions at different lactation stages, and the key phages and bacteria regulating the rumen function and metabolism thus contributing to the milk traits of cows. The potential regulatory roles of phages in affecting the rumen bacteriome suggest that they can be powerful targets for future interventions to improve rumen functions. Video Abstract.

Background: Bovine endometritis is a prevalent uterine disease that directly curtails reproductive performance and indirectly reduces milk production by increasing calving intervals. Postpartum uterine bacterial infection is the primary cause of bovine endometritis, which is typically treated with prostaglandin F2α and antimicrobials. However, abuse of antimicrobials has led to the emergence of multidrug-resistant bacteria, threatening both human and animal health. To explore alternatives to antimicrobial therapy for bovine endometritis, we integrated uterine metagenomic and metabolomic analyses and identified a novel bioactive metabolite with therapeutic potential. The potential antibacterial and anti-inflammatory effects of this metabolite against bovine endometritis were evaluated by assessing its inhibitory effect on the growth of F. necrophorum in vitro, and by quantifying histopathological scores and inflammatory cytokine expression levels in an in vivo mouse model of endometritis, respectively.

Results: A total of 40 Holstein dairy cows at 21 days to 30 days postpartum were assigned into heathy cows (n = 15), subclinical endometritis cows (n = 12) and clinical endometritis cows (n = 13) according to clinical signs and laboratory tests for bovine endometritis. The uterine fluid was collected aseptically for metagenomics and metabolomics sequencing to identify bacterial species associated with bovine endometritis and metabolites that could potentially be used for treatment of bovine endometritis. A total of 17 bacterial species were significantly associated with bovine endometritis, with Fusobacterium necrophorum as the most significantly enriched in cows with clinical endometritis compared to healthy counterparts. In total, 391 metabolites were significantly differentially abundant between healthy and clinical endometritis cows. Among these, a plant-derived compound, tenacissoside G was significantly enriched in healthy cows. Notably, the abundance of F. necrophorum was significantly negatively associated with the concentration of tenacissoside G in clinical endometritis cows. Moreover, tenacissoside G significantly inhibited the growth of F. necrophorum in vitro and ameliorated inflammation in endometritis caused by F. necrophorum in a mice model.

Conclusion: This study provides new insights into the relationship between uterine microbiome and metabolites in bovine endometritis, potentially leading to novel strategies for treating bovine endometritis. Furthermore, tenacissoside G exhibits therapeutic effects against endometritis induced by F. necrophorum, and could serve as a potential alternative to antimicrobials for treating endometritis. Video Abstract.

Background: Carbapenem-resistant hypervirulent K. pneumoniae (CR-HvKP) is a growing public health threat due to its virulence and limited treatment options. While prevalent in hospitals, its presence in livestock, particularly pigs, is poorly understood. The gut microbiome provides colonization resistance, but how it restricts CR-HvKP remains unclear.

Results: To further elucidate the colonization resistance mechanisms of the gut microbiota against CR-HvKP, we analyzed stool samples from piglets (L), nursery (N), fattening (F), and sows (PS) using microbiome modeling (Micolo) and competition assays. ST290 K. pneumoniae isolated from PS inhibited CR-HvKP via carbohydrate competition, with a pronounced effect observed for sucrose. Niche-specific supplementation with methyl pyruvate was found to partially alleviate this ecological inhibitory effect.

Conclusions: Carbohydrate-based interventions could be explored as potential therapeutic or prophylactic strategies to combat CR-HvKP colonization, thereby potentially improving animal and public health outcomes. Video Abstract.

Background: Recent advances in high-throughput approaches for estimating co-localization of microbes, such as SAMPL-seq, allow characterization of the biogeography of the gut microbiome longitudinally and at an unprecedented scale. However, these high-dimensional data are complex and have unique noise properties.

Results: To address these challenges, we developed MCSPACE, a probabilistic AI method that infers, from microbiome co-localization data, spatially coherent assemblages of taxa, their dynamics over time, and their responses to perturbations. To evaluate MCSPACE's capabilities, we generated the largest longitudinal microbiome co-localization dataset to date, profiling spatial relationships of microbes in the guts of mice subjected to serial dietary perturbations over 76 days. Analyses of these data and two existing human longitudinal datasets demonstrated superior benchmarking performance of MCSPACE over existing methods and moreover yielded insights into the spatiotemporal structuring of the gut microbiome, including identifying temporally persistent and dynamic microbial assemblages in the human gut, and shifts in assemblages in the murine gut induced by specific dietary components.

Conclusions: Our results highlight the utility of MCSPACE, which we make available to the community as an open-source software tool, for elucidating the dynamics of microbiome biogeography and gaining insights into the role of spatial relationships in host-microbial ecosystem function. Video Abstract.

Background: The center of sustainable development of grassland husbandry is the balance between forage intake and growth characteristics of animals, and one of the keys to restricting the conversion efficiency of forage intake is the digestibility of forage produced by rumen microorganisms. Thus, the interaction between grass intake and rumen microbial fermentation is a key driver of both ruminant productivity and grassland ecosystem health. However, interactions between grass species, supplementary feeding, rumen microbiome, and rumen epithelium function, remain poorly understood.

Results: We employed metagenomic and metatranscriptomic analyses, coupled with single-cell RNA sequencing (scRNA-seq) of rumen wall and serum metabolomics, to investigate how the rumen microbiome regulates grass intake and host metabolism. In a two-factor (grazing intensity and concentrate supplementation) experiment with 72 lambs, supplementary feeding under moderate grazing increased dry matter intake but decreased grass consumption of Artemisia tanacetifolia. These shifts correlated with contrasting trends between metagenomic and metatranscriptomic profiles of Lachnospiraceae. scRNA-seq revealed an increased abundance of basal cells (BCs), terminally differentiated keratinocytes (TDKs), and differentiated keratinocytes (DKs) in the supplemented group, with solute carrier genes (e.g., SLC16A1) involved in short chain fatty acids (SCFAs) transport enriched in basal cells. We also identified interactions between the rumen microbiome and host epithelial cells, influencing gene expression and localization, which in turn mediated the animal serum nutrient metabolism, particularly in B vitamin, bile acids, and amino acids.

Conclusions: Our study identified key microbiome and epithelial cell subtypes involved in grass digestion and SCFAs metabolism in the rumen. This novel link between ruminal microbial function, epithelial cell cluster-based genes, and host metabolism provides critical insights into mechanisms underlying the interaction between grass intake and supplementary feeding for optimizing ruminant management strategies in sustainable grazing systems. Video Abstract.

Background: Most winter-active mammals experience protein restriction. Gut microbiota is a key regulator of host energy homeostasis during nutrient deficiency, yet cross talk between microbiota and factors (e.g., hormones, signaling molecules) that regulate host energy metabolism in a low-protein (LP) context has not been studied sufficiently.

Result: The LP diet triggered the hepatic FGF21 adaptive metabolic pathway, which increased thermogenesis and reduced body weight, and this adaptive response was dependent on the composition and function of gut microbiota. Specifically, the LP diet induced a reshaping of the gut microbiota, altering its metabolic profile to increase deoxycholic acid levels and thereby increasing UCP1-induced thermogenesis of brown adipose tissue in an FGF21-dependent manner. Fecal transplantation with LP-associated microbiota increased thermogenesis through activation of GCN2-eIF2α-FGF21 signaling. Supplementation of the LP diet with yak fecal bacteria in plateau pika reduced UCP1-associated thermogenesis by altering the gut microbiome, decreasing deoxycholic acid production, suppressing activation of GCN2-eIF2α-FGF21 signaling, and alleviating LP-induced weight loss.

Conclusions: Our study reveals an association between the gut microbiota and LP diet-associated regulation of FGF21 signaling and thermogenesis and further demonstrates that this relationship is influenced by interspecies microbial transfer, indicating a critical mechanism whereby horizontal microbial exchange between sympatric species enhances host energy homeostasis. These findings provide novel insights into our understanding of the adaptations of mammals to high-elevation environments. Video Abstract.

Background: The microorganisms colonizing the gastrointestinal tract of animals, collectively referred to as the gut microbiome, affect numerous host behaviors dependent on the central nervous system (CNS). Studies comparing germ-free mice to normally colonized mice have demonstrated influences of the microbiome on anxiety-related behaviors, voluntary activity, and gene expression in the CNS. Additionally, there is epidemiologic evidence supporting an intergenerational influence of the maternal microbiome on neurodevelopment of offspring and behavior later in life. There is limited experimental evidence however directly linking the maternal microbiome to long-term neurodevelopmental outcomes, or knowledge regarding mechanisms responsible for such effects.

Results: Here we show that that the maternal microbiome has a dominant influence on several offspring phenotypes including anxiety-related behavior, voluntary activity, and body weight. Adverse outcomes in offspring were associated with features of the maternal microbiome including bile salt hydrolase activity gene expression (bsh), abundance of certain bile acids, and hepatic expression of Slc10a1. In cross-foster experiments, offspring resembled their birth dam phenotypically, despite faithful colonization in the postnatal period with the surrogate dam microbiome. Genome-wide DNA methylation analysis of hippocampal DNA identified microbiome-associated differences in DNA methylation of 196 loci in total, 176 of which show conserved profiles between mother and offspring. Further, single-cell transcriptional analysis revealed accompanying differences in expression of several differentially methylated genes within certain hippocampal cell clusters, and vascular expression of genes associated with bile acid transport. Inferred cell-to-cell communication in the hippocampus based on coordinated ligand-receptor expression revealed differences in expression of neuropeptides associated with satiety.

Conclusions: Collectively, these data provide proof-of-principle that the maternal gut microbiome has a dominant influence on the neurodevelopment underlying certain offspring behaviors and activities, and selectively affects genome DNA methylation and gene expression in the offspring hippocampus in conjunction with that neurodevelopment. Video Abstract.