ABSTRACT:CD19 chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for relapsed/refractory diffuse large B-cell lymphoma (R/R-DLBCL), but challenges such as posttreatment failure and immune-related adverse events (AEs) persist. This study explores the gut microbiome as a predictive biomarker for CAR T-cell therapy outcomes and toxicity. Stool and serum samples from patients with R/R-DLBCL were analyzed at apheresis (47 samples) and 1 month after infusion (32 samples) using whole-genome sequencing metagenomics. When compared with healthy controls and newly-diagnosed DLBCL, R/R-DLBCL showed significant gut dysbiosis, characterized by increased Proteobacteria and Enterobacteriaceae. Responders had higher levels of Bacteroides fragilis, whereas nonresponders exhibited higher levels of Faecalibacterium prausnitzii. Functional metagenomic analysis suggested enrichment of inosine biosynthesis pathways in responders, and elevated serum inosine demonstrated an exploratory association with improved progression-free survival. Distinct microbial taxa and serum fatty acid profiles were also linked to CAR T-cell-related AEs, with higher acetate and butyrate levels in patients without AEs and increased isovalerate in those with AEs. These findings indicate that gut microbiome features-particularly Bacteroides fragilis and inosine metabolism-may serve as candidate biomarkers for CAR T-cell therapy outcomes and toxicity. However, given the exploratory nature of these analyses and the limited cohort size, results should be interpreted cautiously. Larger, prospective studies will be required to validate these observations and to assess the potential of microbiome-based strategies to optimize CAR T-cell therapy in R/R-DLBCL.
Oral microorganisms contribute to the progression of oral squamous cell carcinoma (OSCC), and the gut microbiome may also influence OSCC by modulating systemic immunity. This study investigated oral and gut microbial changes in a 4-nitroquinoline N-oxide (4-NQO)-induced OSCC mouse model. After 16 weeks of 4-NQO exposure, significant alterations were observed in the beta diversity of both oral and gut microbiomes. Notably, the relative abundance of Lactococcus increased, especially in oral microbiomes, from week 6 to 16, followed by a decline at week 22, suggesting a 4-NQO-induced niche favorable to its proliferation. Absolute quantification revealed a 4-NQO-induced increase in total bacterial load in the oral cavity, accompanied by elevated absolute abundance of Lactococcus. Unexpectedly, oral administration of Lactococcus strains isolated from 4-NQO-treated mice mildly alleviated inflammation. In vitro, lysates from these strains exhibited protein-dependent cytotoxicity against murine OSCC cells. These results suggest that Lactococcus strains may exert protective effects during OSCC progression.
BackgroundHead and neck cancer, predominantly squamous cell carcinoma, has emerged as a significant global health concern. Growing evidence has established a strong association between dysbiosis of the oral microbiota and both oral and systemic diseases. However, the association between the oral microbiota and head and neck cancer has not yet been fully described. This study aimed to investigate the distinct profiles of the oral microbiota in patients with head and neck cancer and their potential as diagnostic and prognostic biomarkers for head and neck cancer.ResultsComparative analyses revealed that compared to controls, the oral microbiota of patients with head and neck squamous cell carcinoma (HNSCC) exhibited an increased abundance of anaerobic, biofilm-forming bacteria, and potential pathogens. A machine learning model successfully differentiated HNSCC patients from controls with an area under the curve of 0.902. Key features of this model, such as Peptostreptococcus and Capnocytophaga, were found to be candidate biomarkers for HNSCC, with certain taxa, such as Abiotrophia, serving as prognostic indicators. Although pronounced differences in oral microbiota among HNSCC patients primarily resulted from inter-individual variations, distinct community types were identified, with the type dominated by Proteobacteria being associated with the lowest probability of survival.ConclusionsOur findings indicate that the oral microbiota may predict HNSCC and may act as a therapeutic target to improve the prognosis of HNSCC. This investigation underscores the crucial role of oral microbial dysbiosis in the etiopathogenesis and clinical prognosis of HNSCC, making a case for further integrative metagenomic and clinical research.
A novel Gram- stain- positive, facultatively anaerobic, non- motile, catalase- positive, oxidase- negative and ovoid cocci, designated as A1S7(T), was isolated from the gut of a marine sandworm (Alitta virens). Strain A1S7(T )exhibited optimal growth at temperatures of 20-30 degrees C, pH 6-8 and in the presence of 2-4% (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain A1S7(T) belonged to the genus Janibacter, exhibiting a similarity of 99.0% to Janibacter cremeus KACC 20518(T) (98.2%) and Janibacter corallicola KACC 21120(T) (97.2%). The complete genome sequence of strain A1S7(T) revealed a genome size of 3360920 bp with a genomic G+C content of 70.1 mol%. The orthologous average nucleotide identity and the digital DNA-DNA hybridization values between strain A1S7(T) and Janibacter cremeus KCTC 49873(T )were determined to be 89.5 and 37.2%, respectively. The major respiratory quinone was MK- 8(H-4). The predominant fatty acids (>10%) included isoC(16:0), C-17:1 omega 8c, C-18:1 omega 9c and C-17:0. Polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, one unknown phosphoglycolipid and three unknown polar lipids. The cell- wall peptidoglycan type was A1 gamma. The major whole- cell sugars were ribose, mannose and glucose. Based on phenotypic, phylogenetic, genotypic and chemotaxonomic properties, strain A1S7(T) represents a novel species in the genus Janibacter, for which the name Janibacter alittae sp. nov. is proposed. The type strain is A1S7(T) (=KCTC 49714(T) = JCM 36706(T)).
Existing research has underscored the vital interplay between host organisms and their associated microbiomes, which affects health and function. In both plants and animals, host factors critically shape microbial communities and influence growth, health, and immunity. Post-harvest plants, such as those used in kimchi, a traditional Korean dish, offer a unique avenue for exploring host-microbe dynamics during fermentation. Despite the emphasis on lactic acid bacteria (LAB) in fermentation studies, the roles of host factors remain unclear. This study aimed to investigate the influence of these factors on plant transcriptomes during kimchi fermentation. We individually inoculated nine LAB strains into germ-free kimchi to generate LAB-mono-associated gnotobiotic kimchi and performed RNA-sequencing analysis for the host vegetables during fermentation. The transcriptomes of post-harvest vegetables in kimchi change over time, and microbes affect the transcriptome profiles of vegetables. Differentially expressed gene analyses revealed that microbes affected the temporal expression profiles of several genes in the plant transcriptomes in unique directions depending on the introduced LAB strains. Cluster analysis with other publicly available transcriptomes of post-harvest vegetables and fruits further revealed that the plant transcriptome is more profoundly influenced by the environment harboring the host than by host phylogeny. Our results bridge the gap in understanding the bidirectional relationship between host vegetables and microbes during food fermentation, illuminating the complex interplay between vegetable transcriptomes, fermentative microbes, and the fermentation process in food production. The different transcriptomic responses elicited by specific LAB strains suggest the possibility of microbial manipulation to achieve the desired fermentation outcomes.
We isolated three novel strains, S1T, S2T, and S5T, from human oral cavities and identified them as distinct novel species. All these strains are facultatively anaerobic, Gram-stain-positive, and non-flagellated bacteria. Their optimal growth conditions for these strains were observed in Columbia broth (CB) at 37 °C, pH 7.0, and in the absence of NaCl. Phylogenetic analyses, employing the 16S rRNA gene and whole-genome sequencing, confirmed that all three strains belong to the genus Streptococcus. The 16S rRNA gene sequences of strains S1T, S2T, and S5T showed the highest similarities to Streptococcus parasanguinis, 98.57
Purpose For centuries, people have raised money for many purposes, and funding projects utilizing the Internet began to spread in earnest after 2010. However, there is a notable lack of research on crowdfunding projects, especially those involving sports. Given this background, this study's objective is to compare whether motivational factors may work differently depending on crowdfunding type and to analyze the impact of such factors on investments. Design/methodology/approach This study was conducted using stimulation through artificially modified newspaper articles to measure crowdfunding motivation and investment intention. To clarify research questions, this study applied multiple regression analysis. Findings Findings indicate that philanthropic motives and interest in projects influenced the intention to decide on funding and often had positive word-of-mouth effects. In equity-based projects, philanthropic motives and a desire to be recognized acted as drivers for both behaviors. In reward-based projects, philanthropic motives determined investment intentions, and recognition motivation and interest factors influenced word-of-mouth intention. Originality/value This study investigated the motivations and consequent intentions for crowdfunding in the field of the professional sports industry, which had substantive future implications for the business of sports.
Three novel bacterial strains, 321T, 335T, and 353T, were isolated from the intestines of Aegosoma sinicum larvae collected from Paju-Si, South Korea. The strains were Gram-negative, obligate aerobe and had rod-shaped cells with a single flagellum. The three strains belonged to the genus Luteibacter in the family Rhodanobacteraceae and shared < 99.2
PURPOSE This study examined whether K-league fans’ responses to game outcomes align with reference-dependent preference and loss aversion principles. METHODS We collected user comments from the 2023 K-league game highlights videos on YouTube. We identified each user’s supporting team and excluded neutral fans’ comments. Sentiment analysis using KoBERT was applied, and estimated sentiment scores served as dependent variables. We performed panel regression to test whether unexpected wins and losses generate positive and negative comments. RESULTS First, an unexpected win generates more positive comments, and an unexpected loss generates more negative comments; a reference-dependent preference exists. Second, the difference between the coefficient on upset win and the absolute value of the coefficient on upset loss is not statistically different; loss aversion does not exist. CONCLUSIONS The findings derive a deeper understanding of sports viewership and explain the difference between domestic and overseas sports fans. Also, the findings provide insights into the domestic professional sports business.
This study investigates differences in the preferences of daily ticket purchasers and season ticket holders, focusing on outcome uncertainty. Using unique game-level attendance data of both daily ticket purchasers and season ticket holders for every team in the Korean top-tier professional soccer league, we find heterogeneity in demand between daily ticket purchasers and season ticket holders with respect to outcome uncertainty, preference for home team success, team performance, geographical distance between competing teams, and weekend games. Our results suggest that season ticket holders do not care as much about their team's performance and outcome uncertainty as daily ticket purchasers do.
The gut microbiome influences cancer development and the efficacy and safety of chemotherapy, but little is known about its effects on lymphoma. We obtained stool samples from treatment-naïve, newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) (n = 189). We first performed 16S ribosomal RNA gene sequencing (n = 158) and then conducted whole-genome shotgun sequencing (n = 106) with additional samples. We compared the microbiome data from these patients with those of healthy controls and assessed whether microbiome characteristics were associated with treatment outcomes. The alpha diversity was significantly lower in patients with DLBCL than in healthy controls (P < 0.001), and the microbial composition differed significantly between the groups (P < 0.001). The abundance of Enterobacteriaceae family belonging to the Proteobacteria phylum was markedly higher in patients than in healthy controls. Functional analysis of the microbiome revealed an association with opportunistic pathogenesis through type 1 pili, biofilm formation, and antibiotics resistance. Enterobacteriaceae members were significantly enriched in patients who experienced febrile neutropenia and in those who experienced relapse or progression (P < 0.001). Interestingly, greater abundance of Enterobacteriaceae correlated with shorter progression-free survival (P = 0.007). The cytokine profiles of patients whose microbiome was enriched with Enterobacteriaceae were significantly associated with interleukin 6 (P = 0.035) and interferon-g (P = 0.045) levels. In summary, patients with DLBCL exhibited gut microbial dysbiosis. The abundance of Enterobacteriaceae correlated with treatment outcomes and febrile neutropenia. Further study is required to elucidate the origin and role of gut dysbiosis in DLBCL.
This study examines the determinants of competitive advantage with respect to economic performance of sport firms. Logit regressions estimated dependent variables of economic performance measures based on sales per capita of firms. Determinants of competitive advantage were estimated by efficiency indicators, organization characteristic indicators, and industry classification indicators. Increase in efficiency was a significant determinant of competitive advantage as well as organizational type, size of human resource, diversification of products, and sales growth rate. Operationalizing competitive advantage as outperforming the market average and better than the top 10%, the logit regression model provides means for sport firms to analyze industry data to evaluate their own performance. In particular, including efficiency estimates showed practical significance for market analysis.
A novel bacterium, designated strain JHSY0214T, was isolated from the gut of a Korean limpet, Cellana toreuma. Cells of strain JHSY0214T were Gram-stain-negative, strictly aerobic, yellow-pigmented, non-spore-forming, non-motile and showed a rod-coccus growth cycle. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain belonged to the genus Parasphingorhabdus, and was most closely related to Parasphingorhabdus litoris KCTC 12764T (98.71 %). Strain JHSY0214T had two fluoroquinolone-resistance genes and seven multidrug-resistance efflux pump genes, but did not have beta-lactamase genes and zinc resistance genes compared with P. litoris KCTC 12764T. Strain JHSY0214T grew optimally at 30 °C, pH 7.0 and in the presence of 2 % (w/v) NaCl. The predominant cellular fatty acids of strain JHSY0214T were summed feature 8 (C18 : 1 ω6c and/or C18 : 1 ω7c; 41.2 %), summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c; 21 %) and C16 : 0 (18.9 %). The major isoprenoid quinone was ubiquinone-10. The major polar lipids were sphingoglycolipid and phosphatidylethanolamine. The genomic DNA G+C content was 52.8 mol%. Based on phylogenetic, genotypic and phenotypic data, strain JHSY0214T represents a novel species of the genus Parasphingorhabdus, for which the name Parasphingorhabdus cellanae is proposed. The type strain is JHSY0214T (=KCTC 82387T=DSM 112279T).
Three aerobic, Gram-negative, and rod-shaped bacterial strains, designated strains G4M1T, SM13T, and L12M9T, were isolated from the gut of Batillaria multiformis, Cellana toreuma, and Patinopecten yessoensis collected from the Yellow Sea in South Korea. All the strains grew optimally at 25°C, in the presence of 2% (w/v) NaCl, and at pH 7. These three strains, which belonged to the genus Polaribacter in the family Flavobacteriaceae, shared < 98.8% in 16S rRNA gene sequence and < 86.68% in whole-genome sequence with each other. Compared with the type strains of Polaribacter, isolates showed the highest sequence similarity to P. haliotis KCTC 52418T (< 98.68%), followed by P. litorisediminis KCTC 52500T (< 98.13%). All the strains contained MK-6 as their predominant menaquinone and iso-C15:0 as their major fatty acid. Moreover, all the strains had phosphatidylethanolamine as their polar lipid component. In addition, strain G4M1T had two unidentified lipids and three unidentified aminolipids, strain SM13T had three unidentified lipids and three unidentified aminolipids, and strain L12M9T had three unidentified lipids and one unidentified aminolipid. The DNA G + C contents of strains G4M1T, SM13T, and L12M9T were 31.0, 30.4, and 29.7 mol%, respectively. Based on phenotypic, phylogenetic, chemotaxonomic, and genotypic findings, strains G4M1T (= KCTC 82388T = DSM 112372T), SM13T (= KCTC 82389T = DSM 112373T), and L12M9T (= KCTC 62751T = DSM 112374T) were classified into the genus Polaribacter as the type strains of novel species, for which the names Polaribacter batillariae sp. nov., Polaribacter cellanae sp. nov., and Polaribacter pectinis sp. nov., respectively, have been proposed.
Lactic acid bacteria (LAB) in kimchi, a traditional Korean food, are major fermentative microorganisms affecting the quality, safety, and nutritional and organoleptic properties of the final product. In this study, we determined the role of three key LAB strains, Leuconostoc gelidum, Latilactobacillus sakei, Weissella koreensis originated from different raw ingredients during natural fermentation, as opposed to an axenic environment. Starter cultures were inoculated into food with wild indigenous microbial communities, and the dynamics of bacterial communities and metabolites were analyzed during fermentation. As bacteriophages within the food viral community directly affect fermentation by influencing bacterial function and composition, the diversity and composition of DNA viral communities were compared with those of corresponding bacterial communities using a metagenomic approach. Our results provide insights into the ecological role of LAB starters in food fermentation and the potential impact of bacteriophages as modulators of bacterial communities associated with the fermentation properties of kimchi.
Background Invertebrates are a very attractive subject for studying host-microbe interactions because of their simple gut microbial community and host diversity. Studying the composition of invertebrate gut microbiota and the determining factors is essential for understanding their symbiotic mechanism. Cephalopods are invertebrates that have similar biological properties to vertebrates such as closed circulation system, an advanced nervous system, and a well-differentiated digestive system. However, it is not currently known whether their microbiomes have more in common with vertebrates or invertebrates. This study reports on the microbial composition of six cephalopod species and compares them with other mollusk and marine fish microbiomes to investigate the factors that shape the gut microbiota. Results Each cephalopod gut consisted of a distinct consortium of microbes, with Photobacterium and Mycoplasma identified as core taxa. The gut microbial composition of cephalopod reflected their host phylogeny, the importance of which was supported by a detailed oligotype-level analysis of operational taxonomic units assigned to Photobacterium and Mycoplasma. Photobacterium typically inhabited multiple hosts, whereas Mycoplasma tended to show host-specific colonization. Furthermore, we showed that class Cephalopoda has a distinct gut microbial community from those of other mollusk groups or marine fish. We also showed that the gut microbiota of phylum Mollusca was determined by host phylogeny, habitat, and diet. Conclusion We have provided the first comparative analysis of cephalopod and mollusk gut microbial communities. The gut microbial community of cephalopods is composed of distinctive microbes and is strongly associated with their phylogeny. The Photobacterium and Mycoplasma genera are core taxa within the cephalopod gut microbiota. Collectively, our findings provide evidence that cephalopod and mollusk gut microbiomes reflect host phylogeny, habitat, and diet. It is hoped that these data can contribute to future studies on invertebrate-microbe interactions.
Two Gram-stain-negative, mesophilic, strictly aerobic, nonspore forming, and yellow-pigmented strains with rod-shaped cells, designated H21R20T and H23M41T, were isolated from the faeces of an Oriental stork (Ciconia boyciana). Based on 16S rRNA gene sequences, both strains showed the highest similarity (98.3–98.4%) to the type strain of Lysobacter concretionis. Phylogenetic analysis based on the 16S rRNA genes and 92 bacterial core genes showed that strains H21R20T and H23M41T were robustly clustered with L. concretionis Ko07T. Whole genome sequencing revealed that the genomes of both strains were approximately 2.9 Mb in size. The DNA G + C contents of the H21R20T and H23M41T strains were 67.3 and 66.6%, respectively. The two strains showed 80.1–81.7% average nucleotide identity with L. concretionis Ko07T. Strain H21R20T grew optimally at 30°C and pH 8.0 and in the presence of 0.5–3% (wt/vol) NaCl, while strain H23M41T grew optimally at 30°C and pH 7.0–8.0 and in the presence of 0–3% (wt/vol) NaCl. Both strains possessed iso-C15:0, iso-C16:0 and summed feature 9 (iso-C17:1ω9c and/or C16:010-methyl) as the major cellular fatty acids, ubiquinone Q-8 as a predominant quinone, and diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine as the major polar lipids. A multifaceted investigation demonstrated that strains H21R20T and H23M41T represent novel species of the genus Lysobacter, for which we propose the names Lysobacter ciconiae sp. nov. and Lysobacter avium sp. nov. for strains H21R20T (= KCTC 82316T = JCM 34832T) and H23M41T (= KCTC 62676T = JCM 33223T), respectively.
Although several studies have identified a distinct gut microbial composition in Parkinson's disease (PD), few studies have investigated the oral microbiome or functional alteration of the microbiome in PD. We aimed to investigate the connection between the oral and gut microbiome and the functional changes in the PD-specific gut microbiome using shotgun metagenomic sequencing. The taxonomic composition of the oral and gut microbiome was significantly different between PD patients and healthy controls (P = 0.003 and 0.001, respectively). Oral Lactobacillus was more abundant in PD patients and was associated with opportunistic pathogens in the gut (FDR-adjusted P < 0.038). Functional analysis revealed that microbial gene markers for glutamate and arginine biosynthesis were downregulated, while antimicrobial resistance gene markers were upregulated in PD patients than healthy controls (all P < 0.001). We identified a connection between the oral and gut microbiota in PD, which might lead to functional alteration of the microbiome in PD.
In this paper, we investigate competitive balance in Major League Soccer and compare balance across talent acquisition policy regimes with a bias-corrected measure from 1996 to 2019. We evaluate multiple moments of the league talent distribution, and we add to past work by using multiple levels of aggregation that reveal heterogeneous results with respect to the distribution of talent within and across seasons. We show that there has been little improvement in competitive balance over the league's history, though there has been an increase in year-to-year stability in balance and a lower propensity for teams at the extremes of performance.