Yuqiang Nie

Background: Aberrant mucosal immune responses to gut microbiota contribute to inflammatory bowel disease (IBD), yet the mechanisms linking immunoglobulin-coated bacteria to mucosal inflammation remain unclear. Microbial extracellular vesicles (EVs) have emerged as potential modulators of host–microbiota interactions, metabolism, and immunity. This study examined how Lactobacillus johnsonii -derived EVs influence gut microbiota, amino acid metabolism, mucosal T cell polarization—particularly the Th17/Treg balance—and immunoglobulin transport in experimental colitis. Results: Flow cytometry of fecal samples from IBD patients revealed increased IgA-, IgG-, and IgM-coated bacteria. Colonic expression of PIGR and FcRn was also elevated. L. johnsonii was depleted in ulcerative colitis, whereas Proteobacteria and Escherichia _ Shigella were enriched. EVs displayed high structural integrity, gastrointestinal stability, and enhanced accumulation in inflamed colon. In DSS-induced colitis mice, both L. johnsonii and EVs alleviated inflammation, improved histology, reduced pro-inflammatory cytokines, decreased Th17 cells, increased Treg cells, and restored the Th17/Treg balance. These interventions also reduced IgA-, IgG-, and IgM-coated bacteria, lowered fecal immunoglobulins without affecting systemic levels, and downregulated PIGR and FcRn. Multi-omics analyses showed that EVs reshaped gut microbiota, enriched taurine-associated taxa (Lactobacillales, Lactobacillaceae, Lactobacillus murinus ), and elevated the immunoregulatory metabolite taurine, which was linked to sulfur metabolism and epithelial homeostasis. Taurine supplementation reproduced EV effects, including reduced inflammation, improved barrier integrity, Th17/Treg rebalancing, and suppression of PIGR and FcRn. Conclusions: L. johnsonii -derived EVs restore mucosal immune balance in colitis through a coordinated EV–taurine–Th17/Treg–PIGR/FcRn–IgA/IgG axis. By integrating microbiota remodeling, metabolic regulation, and immune modulation—and outperforming the parent bacterium in stability, colonic enrichment, and breadth of effect—these EVs represent promising next-generation biologics for IBD therapy.

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 .

Colorectal cancer (CRC) is a prevalent global malignancy where gut microbiota plays a key role. Streptococcus gallolyticus (Sg), a gut commensal and opportunistic pathogen, is associated with CRC. This study investigates the impact of the supernatant derived from Sg cultures (hereafter referred to as Sgsup) on CRC progression and examines the underlying mechanisms. Quantitative PCR (qPCR) was employed to assess Sg colonization in paired tumors and adjacent normal tissues from 46 CRC patients. CRC cell lines (HCT116, HT29) were treated with Sgsup, and cell proliferation was measured using the CCK-8 assay. Non-targeted metabolomic profiling of Sgsup was performed via liquid chromatography-mass spectrometry (LC-MS). An azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mouse model of CRC was used to evaluate in vivo tumor burden, inflammation, and macrophage polarization (flow cytometry). Transcriptomic analysis via RNA-seq was conducted to identify enriched signaling pathways. The detection rate of Sg was significantly higher in tumor tissues compared to adjacent tissues (47.8% vs. 30.4%, P < 0.01). Sgsup significantly increased CRC cell proliferation (P < 0.05). Non-targeted metabolomic analysis revealed an enrichment of metabolites, including inosine monophosphate (IMP), methionine, uridine, and creatine in Sgsup. In vivo, Sgsup increased tumor number/burden (P < 0.05), elevated inflammation scores (P < 0.05), and shortened colon length. Flow cytometry indicated that Sgsup promoted M2 macrophage polarization (as evidenced by increased CD206+ cells and reduced M1/M2 ratio). RNA-seq demonstrated significant enrichment of the IL-17 signaling pathway, with upregulated expression of IL-17 F and IL-22 (P < 0.05). Sgsup is associated with CRC progression by promoting cell proliferation and inflammation, facilitating M2 macrophage polarization, and elevating IL-17 F and IL-22 expression. Metabolites such as creatine, along with IL-17 F/IL-22-related signaling pathways, appear to be involved. These findings suggest that both Sg-derived metabolites and host immune signaling may serve as potential targets for CRC intervention. Functional validation of individual metabolites is currently in progress.

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.

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.

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.

Background: Plant-derived exosome-like nanoparticles (PELNs) have received widespread attention in treating ulcerative colitis (UC). However, the role of Houttuynia cordata-derived exosome-like nanoparticles (HELNs) in UC remains unclear. This study aims to evaluate the efficacy of HELNs in treating colitis in mice and investigate its potential mechanisms. Methods: HELNs were isolated from H. cordata for characterization, and their safety and stability were evaluated. A dextran sulfate sodium (DSS)-induced colitis mouse model was utilized to assess the therapeutic potential of HELNs in UC. In vivo, imaging and flow cytometry were utilized to investigate the targeting effect of HELNs on inflamed colonic sites and their modulation of the immune environment. RNA-seq analysis and molecular docking were performed to identify potential pathways recruited by HELNs. Guided by transcriptomic findings, NLRP3^−/− mice were used in conjunction with Western blotting, qPCR, immunofluorescence, and other techniques to verify that HELNs alleviated DSS-induced colitis by inhibiting NLRP3/NOD-like receptor signaling pathways. Lastly, the impact of HELNs on the gut microbiota was investigated through 16S rRNA sequencing. Results: HELNs significantly reduced the severity of DSS-induced colitis in mice, alleviating colitis symptoms and histopathological damage. Furthermore, HELNs can specifically target inflamed colon tissue, regulate the immune environment, and decrease inflammation. RNA-seq analysis, coupled with the use of NLRP3^−/− mice, demonstrated that HELNs inhibited the NLRP3/NOD-like receptor signaling pathways. Lastly, HELNs balanced the gut microbiota composition in mice with colitis, decreasing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria in the intestinal tract of these mice. Conclusion: In summary, HELNs exhibit the potential to protect the colon from DSS-induced damage by inhibiting the NLRP3/NOD-like receptor signaling pathway and modulating the gut microbiota, presenting a promising therapeutic option for the management of UC.

The human gut microbiota significantly impacts health, including liver conditions like liver cirrhosis (LC) and spontaneous bacterial peritonitis (SBP). Immunoglobulin A (IgA) plays a central role in maintaining gut microbial balance. Understanding IgA's interplay with gut microbiota and liver health is crucial. This study explores the relationship between fecal IgA levels, gut microbiota, and liver injury severity. A total of 69 LC patients and 30 healthy controls were studied. Fecal IgA levels were measured using ELISA, and IgA‐coated bacteria were quantified via flow cytometry. Microbiota diversity and composition were assessed through 16S rRNA sequencing. Liver injury severity was graded using the Child–Pugh score. Statistical analyses determined correlations. LC patients had higher fecal IgA levels than controls, correlating positively with liver injury severity. Microbiota diversity decreased with severity, accompanied by shifts in composition favoring pro‐inflammatory species. Ralstonia abundance positively correlated with liver injury, whereas Faecalibacterium showed a negative correlation. Specific microbial markers for SBP were identified. Functional profiling revealed altered microbial functionalities in LC and SBP. Elevated fecal IgA levels, coupled with microbiota alterations, correlate with liver injury severity in LC patients. Modulating gut microbiota could be a promising strategy for managing liver‐related conditions. Further research is needed to understand underlying mechanisms and translate findings into clinical practice, potentially improving patient outcomes.