Biology subjects

He, H.

Publications and source records attributed to He, H..

At least 73 records · Page 4Linked to original sources

bioRxiv2024

Inhibition of serine and arginine-rich splicing factor 3 induces epidermal differentiation and decreases cutaneous squamous cell carcinoma risk

Serine/Arginine-rich splicing factor 3 (SRSF3) is one of 12 SRSFs that regulate gene expression via alternative splicing. SRSF3 is upregulated in cutaneous squamous cell carcinoma (cSCC) and several squamous cancer cell lines in relation to normal keratinocytes. We suppressed SRSF3 with a specific inhibitor, SFI003, and observed an increase in epidermal differentiation. Our data suggests that in cSCC, SRSF3 overexpression suppresses cellular differentiation to enable cancer progression. In a clinical setting, patients taking known SRSF3 inhibitors digoxin and amiodarone exhibited higher cSCC-free survival compared to a propensity score-matched cohort treated with beta blockers. Thus, SRSF3 upregulation may be a novel therapeutic target in cSCC that can improve patient prognoses.

cancer biology↗

bioRxiv2024

Building plumbing influences the microdiversity and community assembly of the drinking water microbiome.

Building plumbing microbial communities can significantly influence water quality at the point of use, particularly during periods of stagnation. Thus, a fine-scale understanding of factors governing community membership and structure, as well as environmental and ecological factors shaping building plumbing microbial communities is critical. In this study, we utilized full-length 16S ribosomal RNA (rRNA) gene sequencing to investigate the microdiversity and spatial-temporal dynamics of microbial communities in commercial and residential building plumbing systems. Bacterial operational taxonomic units (OTUs) within commercial buildings exhibited much lower microdiversity relative to the same OTUs in residential buildings. Microdiversity was associated with higher persistence and relative abundance of OTUs. Interestingly, amplicon sequencing variants within the same OTUs exhibited habitat preferences based on the building type while also demonstrating varying temporal turnover patterns. Dispersal limitation disproportionately governed community assembly in commercial buildings, whereas heterogeneous selection was the dominant ecological mechanism shaping the microbial community in residential buildings. Dispersal limitation in commercial buildings is consistent with larger building sizes and greater periods of water stagnation. Interestingly, the inability to explain the extent of heterogeneous selection-driven community assembly in residential locations using measured water chemistry may suggest a disproportionately large effect of fine-scale variation in plumbing characteristics on community assembly in residential locations.

microbiology↗

bioRxiv2024

Cardiac Fibroblasts regulate myocardium and coronary vasculature development via the collagen signaling pathway

The fibroblast (FB), cardiomyocyte (CM), and vascular endothelial cell (Vas_EC) are the three major cell types in the heart, yet their relationships during development are largely unexplored. To address this gap, we employed RNA staining of the FB marker gene Col1a1 together with the CM marker gene Actn2 and the Vas_EC marker gene Cdh5 at different stages. This approach enabled us to discern the anatomical pattern of cardiac FBs and identify approximately one EC and four CMs directly interacting with each FB. Molecularly, through the analysis of single-cell mRNA sequencing (scRNA-seq) data, we unveiled collagen as the top signaling molecule derived from FBs influencing CM and Vas_EC development. Subsequently, we used a Pdgfra-CreER controlled diphtheria toxin A (DTA) system to ablate the FBs at different stages. We found that the ablation of FBs disrupted myocardium and vasculature development and led to embryonic heart defects. Using scRNA-seq, we further profiled the ablated hearts and identified molecular defects in their ventricular CMs and Vas_ECs compared to control hearts. Moreover, we identified a reduction of collagen in the ablated hearts and predicted collagen as the major signaling pathway regulating the differentially expressed genes in the ablated ventricular CMs. Finally, we performed both short-term and long-term fibroblast ablation at the neonatal stage. We found that short-term ablation caused a reduction in collagen and Vas_EC density, while long-term ablation may induce compensatory collagen expression without causing heart function reduction. In summary, our study has identified the function of fibroblasts in regulating myocardium and vasculature development and implicated an important role for the collagen pathway in this process.

developmental biology↗

bioRxiv2024

Immune Cell Influence on Diffuse Large B-Cell Lymphoma: A Mendelian Randomization Analysis

ObjectiveTo elucidate the causal relationship between immune cells and diffuse large B-cell lymphoma (DLBCL), we conducted a Mendelian randomization analysis. MethodsMendelian randomization (MR) leverages genetic variants as instruments to infer causal effects from observational data. Here, we performed a two-sample MR analysis to assess the causal impact of 731 immune cell types on DLBCL. We employed various MR techniques, including the weighted median estimator (WME) and inverse variance weighting (IVW), and conducted sensitivity analyses to ensure result robustness. Additionally, reverse MR analysis was performed to explore the potential causal relationship between DLBCL and immune cells. ResultsWe identified seventeen immune features with causal links to DLBCL, categorized across various cellular groups: four in B cells, two in T cell maturation stages, six in Tregs, four in the TBNK group, and one in dendritic cells (DCs). Sensitivity analyses confirmed the absence of heterogeneity, horizontal pleiotropy, and bias in our findings. Reverse causal analysis revealed a causal association between DLBCL and one of the seventeen immune cell types identified. ConclusionsOur MR analysis of seventeen immune cell types uncovers the complex interactions between the immune system and DLBCL, providing crucial insights into the tumor microenvironment and potential avenues for targeted immunotherapy.

immunology↗

bioRxiv2024

Distinct neural manifolds and critical roles of primate caudate nucleus in multimodal decision-making

Representational redundancy is ubiquitous in the brain with distributed networks encode task variables in a similar way, which may mask the unique roles of each region. Using a multisensory decision paradigm, here we showed that primate caudate nucleus (CN) dramatically differed from decision-related cortices in the reduced low-dimensional neural subspace, although possessing similar choice representations. Specifically, bimodal neural trajectories evolved towards nonvisual (vestibular) in CN, rather than towards visual as in frontal/parietal cortices. This challenges previous hypothesis that striatum mainly reflects cortical decision signals. Following recurrent neural networks simulations suggested that the cortico-subcortical distinction might be due to different intensities of single-modality inputs. We furtherly demonstrated that CN population responses represented the multisensory behavior strategy animal employed within the generalized drift-diffusion framework. Importantly, neural manipulations by unilateral drug injection and microstimulation confirmed CNs causal contributions to multisensory decisions. Overall, our results indicate beyond relay-station in cortico-striatal circuitry, CN plays distinct and critical roles in perceptual decision-making.

neuroscience↗

bioRxiv2024

Expanding the biotechnological scope of metabolic sensors through computation-aided designs

Metabolic sensors are microbial strains modified so that biomass formation correlates with the availability of specific metabolites. These sensors are essential for bioengineering (e.g. in growth-coupled designs) but creating them is often a time-consuming and low-throughput process that can potentially be streamlined by in silico analysis. Here, we present the systematic workflow of designing, implementing, and testing versatile Escherichia coli metabolic sensor strains. Glyoxylate, a key metabolite in (synthetic) CO2 fixation and carbon-conserving pathways, served as the test molecule. Through iterative screening of a compact metabolic model, we identified non-trivial growth-coupled designs that resulted in six metabolic sensors with a wide sensitivity range for glyoxylate, spanning three orders of magnitude in detected concentrations. We further adapted these E. coli strains for sensing glycolate and demonstrated their utility in both pathway engineering (testing a key metabolic module via glyoxylate) and applications in environmental monitoring (quantifying glycolate produced by photosynthetic microalgae). The versatility and ease of implementation of this workflow make it suitable for designing and building multiple metabolic sensors for diverse biotechnological applications. TeaserA streamlined workflow enables the rapid design of versatile E. coli metabolic sensors for detecting key metabolites in bioengineering and monitoring.

synthetic biology↗

bioRxiv2024

AmygdalaGo-BOLT3D: A boundary learning transformer for tracing human amygdala

Each year, thousands of brain MRI scans are collected to study structural development in children and adolescents. However, the amygdala, a particularly small and complex structure, remains difficult to segment reliably, especially in developing populations where its volume is even smaller. To address this challenge, we developed AmygdalaGo-BOLT, a boundary-aware deep learning model tailored for human amygdala segmentation. It was trained and validated using 854 manually labeled scans from pediatric datasets, with independent samples used to ensure performance generalizability. The model integrates multiscale image features, spatial priors, and self-attention mechanisms within a compact encoder-decoder architecture to enhance boundary detection. Validation across multiple imaging centers and age groups shows that AmygdalaGo-BOLT closely matches expert manual labels, improves processing efficiency, and outperforms existing tools in accuracy. This enables robust and scalable analysis of amygdala morphology in developmental neuroimaging studies where manual tracing is impractical. To support open and reproducible science, we publicly release both the labeled datasets and the full source code. TeaserAn AI model enables accurate amygdala segmentation across ages and centers, supporting large-scale brain imaging studies.

neuroscience↗

bioRxiv2024

Computing hematopoiesis plasticity in response to genetic mutations and environmental stimulations

Cell plasticity (CP), describing a dynamic cell state, plays a crucial role in maintaining homeostasis during organ morphogenesis, regeneration and damage-to-repair biological process. Single-cell-omics datasets provide unprecedented resource to empowers analysis on CP. Hematopoiesis offers fertile opportunities to develop quantitative methods for understanding CP with rich supports from experimental ground-truths. In this study we generated high-quality lineage-negative (Lin-) single-cell RNA-sequencing datasets under various conditions and introduced a working pipeline named Snapdragon to interrogate naive and disturbed plasticity of hematopoietic stem and progenitor cells (HSPCs) with mutational or environmental challenges. Utilizing embedding methods UMAP or FA, a continuum of hematopoietic development is visually observed in wildtype where the pipeline confirms a very low Proportion of hybrid-cells (Phc, with bias range: 0.4-0.6) on a transition trajectory. Upon Tet2 mutation, a driver of leukemia, or treatment of DSS, an inducer of colitis, Phc is increased and plasticity of HSPCs was enhanced. Quantitative analysis indicates that Tet2 mutation enhances HSC self-renewal capability while DSS treatment results in an enhanced myeloid-skewing trajectory, suggesting their similar but different consequences. We prioritized several transcription factors (i.e the EGR family) and signaling pathways (i.e. receptors IL1R1 and ADRB, inflammation and sympathy-sensing respectively) which are responsible for Phc alterations. CellOracle-based simulation suggests that knocking-out EGR regulons or pathways of IL1R1 and ADRB partially reverses Phc promoted by Tet2 mutation and inflammation. In conclusion, the study provides high-quality datasets with single-cell transcriptomic matrices for diversified hematopoietic simulations and a computational pipeline Snapdragon for quantifying disturbed Phc and CP. (247 words) HighlightsO_LITo guide CP analysis, we introduce a quantizable parameter Phc and a pipeline Snapdragon, which discriminate naive and disturbed hematopoiesis; C_LIO_LIThe Snapdragon pipeline analysis on Tet2+/-Lin- cells demonstrates many novel insights, including enhanced HSC plasticity and increased PHC; similar trends are observed in inflammatory Lin- cells; C_LIO_LIRegulon analysis suggests that transcriptional factor EGR1 is significantly activated to elevated the HSC plasticity and change hematopoietic trajectory; C_LIO_LIStress-response-related signaling pathways mediated by receptors IL1R1 or ADRB were obviously activated in the challenged hematopoiesis; C_LIO_LICellOracle-based simulation suggests that knocking-out EGR regulons or pathways of IL1R1 and ADRB partially reverses Phc promoted by Tet2 mutation and inflammation. C_LI

developmental biology↗

bioRxiv2024

Branched chain α-ketoacids aerobically activate HIF1α signaling in vascular cells

Hypoxia-inducible factor 1 (HIF1) is a master regulator of numerous biological processes under low oxygen tensions. Yet, the mechanisms and biological consequences of aerobic HIF1 activation by intrinsic factors, particularly in primary cells remain elusive. Here, we show that HIF1 signaling is activated in several human primary vascular cells under ambient oxygen tensions, and in vascular smooth muscle cells (VSMCs) of normal human lung tissue, which contributed to a relative resistance to further enhancement of glycolytic activity in hypoxia. Mechanistically, aerobic HIF activation is mediated by paracrine secretion of three branched chain -ketoacids (BCKAs), which suppress prolyl hydroxylase domain-containing protein 2 (PHD2) activity via direct inhibition and via lactate dehydrogenase A (LDHA)-mediated generation of L-2-hydroxyglutarate (L2HG). Metabolic dysfunction induced by BCKAs was observed in the lungs of rats with pulmonary arterial hypertension (PAH) and in pulmonary artery smooth muscle cells (PASMCs) from idiopathic PAH patients. BCKA supplementation stimulated glycolytic activity and promoted a phenotypic switch to the synthetic phenotype in PASMCs of normal and PAH subjects. In summary, we identify BCKAs as novel signaling metabolites that activate HIF1 signaling in normoxia and that the BCKA-HIF1 pathway modulates VSMC function and may be relevant to pulmonary vascular pathobiology.

cell biology↗

bioRxiv2024

Soybean PHR1-regulated low phosphorus-responsive GmRALF22 increases uptake of phosphate via stimulating GmPTs expression

Phosphorus (P) is one of essential macronutrients for plant growth and development. Rapid Alkalization Factors (RALFs) play crucial roles in plant responses to nutrient stresses, however, the functions of Glycine max RALFs (GmRALFs) under low P (LP) stress remain elusive. In this study, we first identified 27 GmRALFs in soybean, then we revealed that GmRALF10, GmRALF11, and GmRALF22 are induced in both roots and leaves, while only GmRALF5, GmRALF6, and GmRALF25 are up-regulated in leaves in LP conditions. Furthermore, GmRALF22 was found to be the target gene of transcription factor GmPHR1, which binds the P1BS cis-element in the promoter of GmRALF22 via electrophoretic mobility shift assay (EMSA) and DUAL-LUC experiment. Colonization of Bacillus subtilis that deliver GmRALF22 increases the expression of high affinity phosphate (Pi) transporter gene GmPT2, GmPT11, GmPT13 and GmPT14, thus increases the total amount of dry matter and soluble Pi in soybean. RNA-sequencing uncovered that GmRALF22 alleviates LP stress by regulating the expression of JA-, SA- and immune-related genes. Finally, we verified that GmRALF22 is dependent on FERONIA to promote Arabidopsis primary root growth under LP conditions. In summary, GmPHR1-GmRALF22 module positively regulates soybeans tolerance to LP. HighlightsO_LISoybean genome has 27 GmRALFs. GmRALF5, GmRALF6, GmRALF10, GmRALF11, GmRALF22 and GmRALF25 are induced in low phosphorus (LP). C_LIO_LIGmPHR1 directly regulate the transcription of GmRALF22 via binding the promoter P1BS cis-element. C_LIO_LISecretion of GmRALF22 protein by Bacillus subtilis promoted soybean growth under LP conditions by improving soybean P nutrition through increased expression of high affinity phosphate (Pi) transporter gene. C_LIO_LIGmRALF22 regulates soybean P nutrition by JA-, SA- and immune-related genes expression at transcriptome level. That application of GmRALF22 promoted primary root growth in Arabidopsis in LP is dependent on FER receptor. C_LI

molecular biology↗

bioRxiv2024

SASH1 impairs melanin synthesis and metastasis by down-regulating the TGF-β signaling pathway

Dyschromatosis universalis hereditaria (DUH) is a rare genetic dermatosis characterized by widespread hyperpigmentation and depigmentation. In our previous study, we identified SH3 domain-containing protein 1 (SASH1) mutations associated with the DUH phenotype in Chinese families and predict SASH1/THBS1/TGF-{beta}1 signaling to mediate melanin production and melanocyte transport. We detected SASH1/THBS1/TGF-{beta}1 pathway genes expression and evaluated cell phenotypes and melanin synthesis in A375 and PIG1 cell lines by regulating the expression of SASH1 and THBS1 respectively. Finally, we validated the results of the cellular experiments in nude mice. Results showed that SASH1 inhibited the proliferation, migration, invasion, EMT ability and melanin synthesis via TGF-{beta}1 signaling, and THBS1 reversed the elevation of TGF-{beta}1 caused by SASH1 knockdown. We demonstrated that SASH1 further inhibits TGF-{beta}1 through its regulatory effect on THBS1, thereby inhibiting melanin synthesis and metastasis, which may advance the utilization of TGF-{beta}1 for therapeutic purposes. Plain Language SummaryDyschromatosis universalis hereditaria(DUH) is a genetic disease showing uneven pigment pattern, which greatly affects the appearance. In our previous study, we had reported a SASH1 mutation in a Chinese DUH pedigree. In this study, we mainly focus on the effect of SASH1 gene on pigment synthesis and metabolism at the cell and animal level. The results show SASH1 inhibits the melanin synthesis of melanocytes, it can also hinder cell migration, invasion, and EMT. More than that, SASH1 reduced TGF-{beta}1 mRNA, protein expression and promoter activity, and THBS1 could discharge this effect. In mice, SASH1 inhibits the tumor growth via TGF-{beta}1 signaling. We detected a novel SASH1/THBS1/TGF-{beta}1 pathway in cell phenotypes and melanin synthesis.

cell biology↗

bioRxiv2024

Causal network perturbation analysis identifies known and novel type-2 diabetes driver genes

The molecular pathogenesis of type 2 diabetes mellitus (T2DM) involves environmental and genetic factors that remain poorly understood. Increased insulin resistance leads to pancreatic {beta}-islet cell exhaustion and failure, leading to more severe T2DM. As such, targeting {beta}-cell dysfunction is an attractive pathway for T2DM treatment. Single-cell RNA sequencing can help identify differentially expressed genes (DEGs) that may contribute to disease-associated pathophysiology, but cannot capture the full spectrum of disease pathophysiology, as some genes that are not differentially expressed may still play important roles in disease progression or mechanisms. As such, we investigated single-cell gene expression changes in {beta}-cells from healthy (C57BL/6J) and diabetic (NZO/HlLtJ) mice fed with normal or high-fat, high-sugar diet (HFHS) across the spectrum of T2DM development (prediabetic, mild or severely diabetic) using an innovative integration of the causal network perturbation assessment (ssNPA) framework with meta-cell transcriptome analysis to identify driver genes for T2DM. By generating a reference causal network and conducting in silico perturbations, we identified three classes of genes implicated in T2DM pathophysiology: (1) DEGs that were not perturbed (e.g, Igf2bp2 strongly linked to {beta} cell dysfunction and glucose regulation), (2) perturbed non-DEGs (e.g., Glp1r a therapeutic target of modern diabetes drugs) that were perturbed, and (3) DEGs that were perturbed (e.g., Pdx1 a master {beta} cell transcription factor), and validated some of the targets using the KOMP database. Together, these results show that each analytic layer captures complementary mechanisms underlying T2DM severity, and their synthesis provides a more complete view of the disease pathophysiology.

bioinformatics↗

bioRxiv2024

Single-cell landscapes of long non-coding RNAs in early vascular endothelial development and hemogenic specification

Understanding the molecular regulation of arterial and hemogenic specification during early embryonic vascular development is crucial for guiding vascular and hematopoietic regeneration. Accumulating evidence emphasizes the role of long non-coding RNAs (lncRNAs) in cell fate decision. However, the dynamic expression and the potential roles of lncRNAs in early vascular development are still unknown. Here, we first constructed a single-cell landscape of lncRNA expression based on the deeply sequenced tag-based single-cell transcriptome data of early embryonic vascular endothelial cells (VECs). We revealed the contribution of lncRNAs to VEC heterogeneity and identified 295 lncRNAs with specific expression in eight VEC populations. Furthermore, we identified a series of lncRNAs potentially involved in regulating the two waves of arterial specification and hemogenic specification. We uncovered a transient downregulation of H19 in the hemogenic endothelial population during endothelial-to-hematopoietic transition. Additionally, we constructed a transcription factor regulatory network composed of 287 regulons for early VEC development. We further revealed differential activation patterns of regulons and modules in the eight VEC populations, and predicted potential lncRNA-regulon regulatory network. Moreover, unsupervised analysis of the lncRNA expression profile revealed novel VEC subpopulations strongly associated with the maturation of VECs, suggesting the prominent roles of lncRNAs in endothelial maturation. In summary, our study fills the gap in understanding of lncRNA regulatory networks in early vascular development and provides insights into the fields of vascular and hematopoietic regeneration research.

developmental biology↗

bioRxiv2024

Characterizing interactions of ER resident proteins in situ through the YST-PPI method

The mutual interactions of ER resident proteins in the ER maintain its functions, prompting the protein folding, modification, and transportation. Here, a new method, named YST-PPI (YESS-based Split fast TEV protease System for Protein-protein Interaction) was developed, targeting the characterization of protein interactions in ER. YST-PPI method integrated the YESS system, split-TEV technology and endoplasmic reticulum retention signal peptide (ERS) to provide an effective strategy for studying ER in situ PPIs in a fast and quantitative manner. The interactions among 15 ER resident proteins of S. cerevisiae were explored using the YST-PPI system, and their interaction network map was constructed, in which more than 74 interacting resident protein pairs were identified. Our studies also showed that Lhs1p plays a critical role in regulating the interactions of most of the ER resident proteins, expect the Sil1p, indicating its potential role in controlling the ER molecular chaperones. Moreover, the mutual interaction revealed by our studies further confirmed that the ER resident proteins perform their functions in a synergetic way and multimer complex might be formed during the process.

microbiology↗

bioRxiv2024

Human birth tissue products as a regenerative medicine to inhibit post-surgical pain through multi-modal action

Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain. Local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO-induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3 induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain. Moreover, we unravel the underlying mechanisms of pain inhibition induced by FLO and HC-HA/PTX3.

neuroscience↗

bioRxiv2024

MBL-1/Muscleblind regulates neuronal differentiation and controls the splicing of a terminal selector in Caenorhabditis elegans

The muscleblind family of mRNA splicing regulators is conserved across species and regulate the development of muscles and the nervous system. However, how Muscleblind proteins regulate neuronal fate specification and neurite morphogenesis at the single-neuron level is not well understood. In this study, we found that the C. elegans Muscleblind/MBL-1 promotes axonal growth in the touch receptor neurons (TRNs) by regulating microtubule stability and polarity. Transcriptomic analysis identified dozens of MBL-1-controlled splicing events in genes related to neuronal differentiation or microtubule functions. Among the MBL-1 targets, the LIM-domain transcription factor mec-3 is the terminal selector for the TRN fate and induces the expression of many TRN terminal differentiation genes. MBL-1 promotes the splicing of the mec-3 long isoform, which are essential for TRN fate specification, and inhibits the short isoforms that have much weaker activities in activating downstream genes. MBL-1 promotes mec-3 splicing through three "YGCU(U/G)Y" motifs located downstream of the included exon, which is similar to the mechanisms used by mammalian Muscleblind and suggests a deeply conserved context-dependency of the splicing regulation. Interestingly, the expression of mbl-1 in the TRNs is dependent on the mec-3 long isoform, indicating a positive feedback loop between the splicing regulator and the terminal selector. Finally, through a forward genetic screen, we found that MBL-1 promotes neurite growth partly by inhibiting the DLK-1/p38 MAPK pathway. In summary, our study provides mechanistic understanding of the role of Muscleblind in regulating cell fate specification and neuronal morphogenesis.

developmental biology↗

bioRxiv2024

Location of phosphorylation sites within long polypeptide chains by binder-assisted nanopore detection

The detection and mapping of protein phosphorylation sites are essential for understanding the mechanisms of various cellular processes and for identifying targets for drug development. The study of biopolymers at the single-molecule level has been revolutionized by nanopore technology. In this study, we detect protein phosphorylation within long polypeptides (>600 amino acids), after the attachment of binders that interact with phosphate monoesters; electro-osmosis is used to drive the tagged chains through engineered protein nanopores. By monitoring the ionic current carried by a nanopore, phosphorylation sites are located within individual polypeptide chains, providing a valuable step toward nanopore proteomics.

biochemistry↗

bioRxiv2024

Cyclocarya paliurus polysaccharides improve high fat diet-fed mice lipid dysmetabolism through gut microbiota

Obesity is associated with low-grade chronic inflammation and intestinal dysbiosis. Cyclocarya paliurus (C. paliurus) has been shown to improve lipid metabolism and gut microbiota communities in animals and humans; however, it remains to know whether Cyclocarya paliurus polysaccharides (CCPP) prevents obesity through gut microbiota. Here, we found that high fat diet promoted the lipid accumulation and intestinal microbiota dysbiosis in mice, while drink Cyclocarya paliurus polysaccharides reduces body weight, inflammation, alleviated the lipid accumulation, and reversed gut microbiota dysbiosis, including the diversity of intestinal microbiota, relative abundances of Lachnospiraceae. By transplanting faeces from CP-treated mice to HFD-fed mice, the effects of anti-obesity and microbiome regulation can be transferred through gut microbiota. Our results indicate that Cyclocarya paliurus polysaccharides can prevent gut dysbiosis and obesity-related metabolic disorders in obese individuals, the mechanism is related to the remodeling of intestinal flora.

microbiology↗