The gut microbiota contributes to inflammatory bowel disease (IBD) pathogenesis, yet the functional impact of specific bacterial species remains unclear. Here, Odoribacter splanchnicus (O. splanchnicus) is indentified as a taxon depleted in human IBD cohorts and demonstrated its protective effects in acute and chronic murine colitis models. In mice, O. splanchnicus administration alleviated colonic inflammation and preserved barrier integrity, accompanied by a restructured mucosal immune landscape and reduced neutrophil extracellular traps (NETs) formation. This inhibitory effect on NETs is lost in Pad4-/- mice, highlighting its dependence on NETs formation machinery. Metabolomic profiling showed that O. splanchnicus treatment elevated the secondary bile acid lithocholic acid (LCA). This increase is lost following antibiotic cocktail treatment and restored by fecal microbiota transplantation from O. splanchnicus-treated donors, demonstrating a requirement for an intact gut microbiota. Mechanistically, LCA supplementation recapitulated the anti-NETs formation phenotype and suppressed colonic inflamation by inhibiting the NLRP3-GSDMD signaling pathway. Together, these findings define a gut microbiota-metabolite-neutrophil axis in IBD pathogenesis, highlighting the microbiota-dependent regulation of LCA as a key protective mechanism of O. splanchnicus.
BACKGROUND AND AIM:Peroxisome proliferator-activated receptors (PPARs), as nuclear receptors, modulate both lipid metabolism and inflammatory/immune processes. This study examines the impact of modulating the activities of the PPAR subtypes PPARβ/ð and PPARγ on the gut microbiota in inflammatory bowel disease (IBD). METHODS:Mice with dextran sulfate sodium (DSS)-induced acute colitis were treated with the PPARγ agonist pioglitazone, PPARβ/δ agonist GW0742, or their respective antagonists (GW9662, GSK3787). Weight loss, diarrhea severity, hematochezia, and disease activity index were assessed daily. Upon study completion, colon length, histopathology, and mRNA levels of the intestinal barrier and inflammatory markers were measured. Occludin and E-cadherin levels were assessed via immunofluorescence analysis, and cecal samples underwent 16S rRNA sequencing for gut microbiota analysis. RESULTS:Our findings revealed that the agonists pioglitazone and GW0742 effectively suppressed DSS-induced colitis, improved clinical symptoms, reversed colon shortening, and mitigated histological damage. Conversely, their antagonists, GW9662 and GSK3787, failed to alleviate inflammation and sometimes exacerbated disease indicators. Both agonists modulated DSS-induced dysbiosis by reducing the abundance of proinflammatory cytokine-associated microbiota, including Bacteroides, Enterococcus, and Escherichia-Shigella, while enhancing both α-diversity and β-diversity of the gut microbiome, to restore equilibrium. CONCLUSION:Our findings reveal that activation of PPARγ and PPARβ/δ can balance the gut microbiota in mice and ameliorate experimental colitis in mice. Thus, PPARγ and PPARβ/δ have protective effects against IBD and could serve as novel therapeutic targets for its treatment.
Metabolic processes of aquatic photosynthetic organisms significantly influence the multi-time scale cycle of dissolved inorganic carbon (DIC) in aquatic environments. Running karst water characterized by high DIC content are becoming lentic water body due to damming activities around the world, which could benefit for aquatic metabolic processes and change initial carbon cycle processes. However, despite the availability of high-resolution monitoring data, there is a lack of comprehensive studies examining the characteristics of the metabolic processes of aquatic photosynthetic organisms, controlling factors, and their relationship with changes in reservoir thermal structure and carbon cycling. Based on this, this study selected the Dalongdong (DLD) reservoir, a typical karst reservoir located in Southwest China, as the research area for multi-parameter high-resolution continuous monitoring conducted in 2021. Seasonal sampling of relevant indicators was conducted in June, August, and December. The results indicate that the average net ecosystem production (NEP) of surface-layer during mixing period was 0.40 mg L-1 d-1, significantly lower than the thermal stratification period (4.65 mg L-1 d-1). The reservoir demonstrated a net autotrophic state, with the estimated carbon sink of approximately 81.54 t C km-2 y-1. Seasonal and diurnal variations in metabolic processes were primarily influenced by photosynthetically active radiation, which subsequently affected the hydrochemical characteristics. During the thermal stratification period, high temperatures and significant DIC fertilization effect sustained high production efficiency among aquatic photosynthetic organisms. In contrast, during the mixing period, biological growth was more dependent on upwelling nutrient inputs from the reservoir bottom. Through physical disturbances and the inhibition of biological photosynthesis, CO2 emissions increased during rainfall, while NEP rose following the rainfall. Combining high-resolution continuous data with seasonal sampling data, the multi-scale effects of aquatic photosynthetic metabolism on the carbon cycle in aquatic systems are elucidated, which is essential for accurately calculating the carbon budget in reservoir basins.
As an important intestinal microorganism, Odoribacter splanchnicus frequently appears in high-throughput sequencing analyses, although pure culture research on this microorganism is not as advanced. It is widely present in the mammalian gut and is closely associated with the health status of the host and the incidence of various diseases. In recent years, changes in the abundance of O. splanchnicus have been found to be positively or negatively correlated with health issues, such as obesity, metabolic syndrome, diabetes, and intestinal inflammation. It may exhibit a dual protective or promotional role in specific diseases. Thus, it may play an important role in regulating host metabolism, immune response, and intestinal homeostasis. Additional research has revealed that O. splanchnicus can synthesize various metabolites, especially short-chain fatty acids (SCFAs), which play a key role in promoting intestinal health, enhancing energy metabolism, improving insulin resistance, and regulating immune responses in the host. Therefore, O. splanchnicus is a strong candidate for “next-generation probiotics”, and its potential probiotic function provides novel ideas for the development of functional foods and the prevention and treatment of metabolic and intestinal inflammatory diseases. These findings can help develop new biological treatment strategies and optimize health management plans.
Faecalibacterium prausnitzii is a major commensal bacterium that plays a crucial role in intestinal homeostasis. Its secretes an microbial anti-inflammatory molecule (MAM) that functions as a potential therapeutic agent in inflammatory bowel disease (IBD). However, the molecular mechanisms through which MAM exerts its beneficial effects remain incompletely understood. Here, we investigate whether MAM modulates autophagy and to evaluate its therapeutic potential in a murine model of colitis. A genetically engineered Lactococcus lactis strain expressing MAM was administered to mice with dextran sulfate sodium (DSS)-induced or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. The therapeutic effects of MAM were evaluated using clinical scoring, histopathological analysis, and inflammatory cytokines measurement. Intestinal barrier function was assessed based on tight junction protein expression. Autophagy-related signaling pathways were analyzed using western blotting and immunohistochemistry. To determine how autophagy affects MAM, DSS-treated mice were treated with the autophagy inhibitor hydroxychloroquine (HCQ) and bafilomycin A1 (BafA1). Gut microbiota composition was profiled 16 S rRNA gene amplicon sequencing. Fecal short-chain fatty acid (SCFA) levels were quantified by gas chromatography–mass spectrometry (GC-MS). MAM treatment significantly alleviated colitis in both DSS- and TNBS-induced models, as evidenced by reduced disease activity, improved colon length, attenuated histopathological damage, and decreased pro-inflammatory cytokine production. MAM enhanced intestinal barrier integrity by upregulating ZO-1 and occludin. Notably, MAM counteracted the inhibitory effect of HCQ/BafA1 on autophagy, enhancing autophagic flux despite autophagy suppression. Furthermore, MAM treatment significantly increased the fecal concentrations of acetate, propionate, and butyrate. 16 S sequencing revealed the enrichment of beneficial taxa, including Lactobacillus and Lachnospiraceae_NK4A136_group, The abundance of these taxa was positively correlated with SCFA levels and improvement of colitis symptoms. We identified MAM as a multifunctional microbial effector with potent anti-inflammatory properties. MAM improves intestinal barrier function and attenuates experimental colitis through dual mechanisms involving the modulation of autophagy and gut microbiota composition. These findings highlight the translational potential of MAM and support further investigation into its use as a novel therapeutic strategy for IBD.
Gut microbiota and their metabolites play a significant role in inflammatory bowel disease. Here, we attempted to determine the anti-inflammatory role of the probiotic Clostridium. butyricum (CB) in inflammatory bowel disease and identify the exact immune mechanism. The clinical significance of Clostridiales and CB was explored in patients with ulcerative colitis. The inflammation-suppressive role of CB was evaluated in mice with DSS-induced colitis. 16S rRNA sequencing was performed to assess changes in the gut microbiota. Altered transcription levels were detected by RNA sequencing. Flow cytometry was performed to assess the frequency of IgA responses to gut microbiota. Clostridiales and CB were depleted in ulcerative colitis. Oral gavage with CB significantly suppressed weight loss and colon shortening in the dextran sulfate sodium-induced colitis mouse model. Intestinal barrier injury was reversed and the gut microbiota was restored upon treatment with CB administration. The mucosal immune response to gut microbiota was reversed upon treatment with CB. CB conditional medium was more effective than heat-killed CB in alleviating inflammation. Mechanistically, retinol metabolism and retinoic acid levels were higher in groups treated with CB and butyrate. CB and the metabolite butyrate exerted a suppressive role on the abundance of Immunoglobulin A-coated gut microbiota by inhibiting retinoic acid synthesis. In summary, CB protects against inflammation and intestinal barrier injury by producing anti-inflammatory metabolites that can regulate the mucosal immune response to gut microbiota by increasing retinoic acid levels in the colon.
Recalcitrant dissolved organic carbon (RDOC) generated by microbial carbon pumps (MCP) significantly influences terrestrial waters and may contribute to the formation of a long-lasting carbon sink. However, there remains a notable lack of research on the carbon fixation processes and efficiencies of MCP in response to changes in thermal structure within subtropical reservoirs. In this study, we examined the effectiveness of transforming dissolved inorganic carbon (DIC) into dissolved organic carbon (DOC) and subsequently into RDOC through the influence of MCP at various water depths during both Thermal stratification (TS) periods and Mixing (MX) period in the Dalongdong (DLD) Reservoir, a representative subtropical reservoir. The findings indicate that the conversion efficiency of microbiologically recalcitrant dissolved organic carbon (MRDOC) was typically four times greater during the TS periods compared to the MX period. This increase can be attributed to a higher abundance of bacteria involved in carbon fixation, as well as elevated levels of external semi-labile dissolved organic carbon (SLDOC) and labile dissolved organic carbon (LDOC), along with the accumulation of organic matter. Notably, the conversion efficiency peaked in the thermocline during the Obvious thermal stratification (OTS) period. During the TS periods, heterotrophic and chemoautotrophic bacteria played a significant role in carbon fixation in the epilimnion and thermocline, while fewer bacteria were engaged in carbon fixation in the hypolimnion. Conversely, throughout the MX period, the effects of water temperature and pH result in a diminished role of autotrophic bacteria in carbon fixation, leading to a decline in MRDOC conversion efficiency at all water layers. These results enhance our understanding of the carbon cycling processes influenced by the MCP effect in terrestrial waters experiencing changes in thermal stratification.
Microcystis bloom is the most common harmful bloom.Microcystis cells in bloom aggregate into colonies,which is crucial for maintaining their ecological advantage.Dispersing Microcystis into the unicellular form can decrease their competitive advantage,and has been used as a strategy to control Microcystis bloom.In this study,five polysaccharide-degrading bacteria(PDB)with the a-bility to decompose the extracellular polysaccharides of Microcystis were screened by using bacterial polysacchrides xanthan gum and the extracellular polysaccharides of Microcystis flos-aquae as the carbon sources.The effects of the bacteria on the extracellular poly-saccharides of unicellular strain M.flos-aquae,and on the colony size of colonial strain M.wesenbergii were observed by co-culture.The results showed that four strains of bacteria were able to significantly reduce the viscosity of the extracellular polysaccharides of M.flos-aquae.All five strains were able to reduce the colonial size and to inhibit the growth of M.wesenbergii.The PDB were identified to the genus Pseudomonas by 16S rDNA.This study showed that the PDB have the potential to control Microcystis bloom.
Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is considered significant global health concerns worldwide. Many studies have demonstrated that environmental and dietary factors influence the gut microbiota, which in turn orchestrates the host immune responses. These interactions are also involved in complex metabolic processes that contribute to the pathogenesis of IBD. Furthermore, recent studies in genomics and metabolomics have unveiled the intricate relationship between microbial influencers and host epigenetics. The dynamics of gut microbiota and its metabolites intricately align with DNA methylation, histone methylation, lactylation, glycosylation, and non-coding RNAs, which are key players in epigenetics. Here, we summarize and discuss the complex interplay among gut microbiota, epigenetics, and environmental and dietary factors, and their impact on the pathogenesis of IBD. Furthermore, we highlight the importance of multi-omics technologies in dissecting the host-microbe interactions in IBD, potentially offering a framework for developing effective treatment strategies.
Background Plant-derived exosome-like nanoparticles (PELNs) have been considered to have great prospects in the treatment of ulcerative colitis (UC) as they serve as a natural nano-drug carrier that can improve drug stability and cellular uptake. In this study, we isolated Houttuynia cordata-derived exosome-like nanoparticles (HELNs) from Houttuynia cordata and preliminarily explored the protective effect of HELNs on sodium dextran sulfate (DSS) induced colitis model. Methods HELNs were isolated from Houttuynia cordata using sucrose density gradient centrifugation.18 BALB/c mice were randomly divided into Ctrl (regular water), DSS (3.0% DSS water), and DSS+HELNs (DSS water + HELNs) groups. The mice were monitored daily for their body weights, stool consistency, and the presence of blood in the anus or stool. At the end of the experiment, their colon tissue was dissected. The colon lengths were measured, and the dissected tissues were collected for qPCR and pathology. Results After HELNs intervention, diarrhea, bloody stool and weight loss in colitis mice were alleviated (p<0.01). Disease activity index (DAI) score (p=0.0229) decreased, and colon length (p<0.01) improved. Compared with the DSS group, the pathological damage to the colon in the DSS+HELNs group was milder, which was mainly manifested by intact colonic mucosal structure and crypt structure, less inflammatory cell infiltration, and more goblet cells. Compared with the DSS group, the relative mRNA expression of pro-inflammatory cytokines (TNF-α and IL-6) was decreased (p<0.0001; p<0.0001), the relative expression level of anti-inflammatory cytokine IL-10 increased (p=0.0386), while the expression of tight junction protein of occlusion band protein-1 (ZO-1), occlusin-1 and mucin-2 (MUC2) increased (p=0.0341; p=0.0267). (IDDF2024-ABS-0118 Figure 1. Oral administration of HELNs protects mice from DSS-induced colitis, IDDF2024-ABS-0118 Figure 2. Transmission electron microscopy (TEM) images of HELNs and characterization of HELNs.; p<0.0001) Conclusions We first explored the use of HELNs in experimental colitis and found that HELNs play a therapeutic role by reducing the expression of inflammatory cytokines and promoting the restoration of intestinal barrier function.
Accurate remote sensing estimates of inland water colored dissolved organic matter (CDOM) are dramatically challenged by the dynamics of bio-optical characteristics, in which water biochemical driving mechanisms are particularly complex and highly variable. Actually, many of the empirical relationships in the inland water CDOM algorithms are only applicable to specific waters, and they are extremely susceptible to changes in phytoplankton and sediment. This study obtains a classification of bio-optical properties based on spectral shape and constructs a methodology for optically heterogeneous datasets to dynamically monitor CDOM in water. The reliability of the classification algorithm is validated using measured dataset and Global Reflectance community dataset for Imaging and optical sensing of Aquatic environments (GLORIA dataset) (ag(443) varying from 0.001 m-1 to 25.14 m-1). The results show that retrieved CDOM absorption has an improved performance with a mean absolute percentage error (MAPE) of 38.69 % for measured dataset and 43.29 % for GLORIA dataset, respectively. Drivers of CDOM in inland waters can be illustrated on the basis of bio-optical types, CDOM levels, and CDOM source characteristics produced by satellite sensors.
Background Probiotics are a potentially effective therapy for inflammatory bowel disease (IBD); IBD is linked to impaired gut microbiota and intestinal immunity. However, the utilization of an antibiotic cocktail (Abx) prior to the probiotic intervention remains controversial. This study aims to identify the effect of Abx pretreatment from dextran sulfate sodium (DSS)-induced colitis and to evaluate whether Abx pretreatment has an enhanced effect on the protection of Clostridium butyricum Miyairi588 (CBM) from colitis. Results The inflammation, dysbiosis, and dysfunction of gut microbiota as well as T cell response were both enhanced by Abx pretreatment. Additionally, CBM significantly alleviated the DSS-induced colitis and impaired gut epithelial barrier, and Abx pretreatment could enhance these protective effects. Furthermore, CBM increased the benefit bacteria abundance and short-chain fatty acids (SCFAs) level with Abx pretreatment. CBM intervention after Abx pretreatment regulated the imbalance of cytokines and transcription factors, which corresponded to lower infiltration of Th1 and Th17 cells, and increased Th2 cells. Conclusions Abx pretreatment reinforced the function of CBM in ameliorating inflammation and barrier damage by increasing beneficial taxa, eliminating pathogens, and inducing a protective Th2 cell response. This study reveals a link between Abx pretreatment, microbiota, and immune response changes in colitis, which provides a reference for the further application of Abx pretreatment before microbiota-based intervention.
Revealing the subtle variations in thermal structure in a reservoir is crucial for accurately understanding the interaction between water and the carbon cycle. This study provides a detailed description of the thermal structure of Dalongdong reservoir, a representative subtropical stratified reservoir in Guangxi, China. It unveils the three stable state changes in water - mixing, microstratification, and stratification - along with their influencing factors. The study emphasizes air temperature (AT) as the primary factor influencing water temperature (WT) stability, followed by water level. Cross-correlation analysis shows that adjacent WTs experience a prolonged response hysteresis during the stratification period, while the mixing period exhibits a shorter hysteresis. Wavelet analysis revealed that AT and surface-layer WT exhibited a dominant oscillation period of 16-32 h. The periodicity of other water layers is not obvious. This framework can help to enhance our understanding of material cycles and protection of the water environment.
Background The prevalence of inflammatory bowel disease (IBD) has been on the rise in developing countries. However, the mechanism of interaction between gut microbiota and immunity, especially how probiotics regulate the imbalance of mucosal immunity in IBD, remains unclear. Hence, this study aims to explore the role of Clostridium butyricum (C. butyricum) in M2 macrophage-mediated intestinal barrier injury repairation regarding the mechanism of efferocytosis. Methods C. butyricum was treated in DSS-induced colitis mice to observe the gut barrier and the macrophage phenotype (IDDF2024-ABS-0252 Figure 1. C. butyricum promoted polarization and efferocytosis of macrophage in colitis mice (A) The flow chart of the experiment). The efferocytosis-related gene expression in terms of mucosal healing was explored in colitis mice with or without clodronate liposome treatment. RNA-sequencing was used to study the mechanism of C. butyricum on macrophage efferocytosis. Results We found that C. butyricum relieved intestinal inflammation and intestinal barrier injury in colitis mice (IDDF2024-ABS-0252 Figure 1. C. butyricum promoted polarization and efferocytosis of macrophage in colitis mice (B,C) The wight loss and histological images of mice). M2 macrophages and the efferocytosis-related genes were upregulated after C. butyricum treatment (IDDF2024-ABS-0252 Figure 1. C. butyricum promoted polarization and efferocytosis of macrophage in colitis mice (D-I) The frequency and efferocytosis-related genes expression of macrophage). Macrophage deletion induced by clodronate liposomes prevented the role of C. butyricum on the intestinal barrier and macrophage phenotype (IDDF2024-ABS-0252 Figure 1. C. butyricum promoted polarization and efferocytosis of macrophage in colitis mice (J-M) The effect of C. butyricum after macrophage clearance). RNA-sequencing revealed differentially expressed genes upregulated and downregulated (IDDF2024-ABS-0252 Figure 2. The role of C. butyricum on inflammation suppression and efferocytosis was mediated PPAR╬│ activation (A) The numbers of differentially expressed genes after C. butyricum treatment). KEGG enrichment results suggested that the PPAR pathway were significantly enriched and the expression of PPAR pathway-related genes was identified (IDDF2024-ABS-0252 Figure 2. The role of C. butyricum on inflammation suppression and efferocytosis was mediated PPAR╬│ activation (B,C) The result of enrichment analysis and differentially expressed genes that enriched in PPAR pathway). C. butyricum upregulated the expression of PPARδ and PPARγ, not PPARα (IDDF2024-ABS-0252 Figure 2. The role of C. butyricum on inflammation suppression and efferocytosis was mediated PPAR╬│ activation (D-F) The relative expression of genes). Furthermore, PPARγ inhibitor GW9662 instead of PPARδ inhibitor GSK3787 could prevent the role of C. butyricum in inflammation suppression and macrophage efferocytosis promotion (IDDF2024-ABS-0252 Figure 2. The role of C. butyricum on inflammation suppression and efferocytosis was mediated PPAR╬│ activation (G,H) The weight loss and colon length of mice). Conclusions Our findings demonstrated that C. butyricum attenuated intestinal inflammation and barrier injury by promoting M2 macrophage polarization and efferocytosis, which is partly mediated by PPARγ activation.