Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1.

BACKGROUND: Bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, inhibits angiogenesis and reduces tumor growth. Serum VEGF-C, lactate dehydrogenase, and inflammatory markers have been reported as predictive markers related to bevacizumab treatment. Programmed cell death ligand 1 (PD-L1) could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis. AIM: To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer (CRC) according to the expression of PD-L1. METHODS: This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24, 2014 and February 28, 2022, at Samsung Medical Center (Seoul, South Korea). Analysis of patient data included evaluation of PD-L1 expression by the combined positive score (CPS). We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC. RESULTS: A total of 124 patients was included in this analysis. Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy. While 77% of patients received FOLFOX, 23% received FOLFIRI as backbone first-line chemotherapy. The numbers of patients with a PD-L1 CPS of 1 or more, 5 or more, or 10 or more were 105 (85%), 64 (52%), and 32 (26%), respectively. The results showed no significant difference in progression-free survival (PFS) and overall survival (OS) with bevacizumab treatment between patients with PD-L1 CPS less than 1 and those with PD-L1 CPS of 1 or more (PD-L1 < 1% vs PD-L1 ≥ 1%; PFS: P = 0.93, OS: P = 0.33), between patients with PD-L1 CPS less than 5 and of 5 or more (PD-L1 < 5% vs PD-L1 ≥ 5%; PFS: P = 0.409, OS: P = 0.746), and between patients with PD-L1 CPS less than 10 and of 10 or more (PD-L1 < 10% vs PD-L1 ≥ 10%; PFS: P = 0.529, OS: P = 0.568). CONCLUSION: Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Determination of biogenic amine-producing lactic acid bacteria in kimchi varieties through in vitro analysis and low temperature fermentation.

This study analyzed biogenic amine (BA) content in three varieties (types) of kimchi (Baechu kimchi, Baek kimchi, and Yeolmu kimchi), identified the causative bacteria, and evaluated the gene expression associated with the BA formation during kimchi fermentation at 4 °C. Histamine content exceeding the toxicity limit was detected in a single Baechu kimchi product. Tyramine content in most Baechu kimchi products was approximately half of the toxicity limit. Other varieties had relatively lower BA content. Most BA producers isolated from all kimchi varieties were identified as Levilactobacillus brevis, which prominently produced tyramine. To clarify the role of L. brevis in tyramine formation in Baechu kimchi, fermentation experiments were performed using L. brevis BC1M20. The results showed that tyramine content and tyrosine decarboxylase gene (tdc) expression were higher in the inoculated kimchi than in the control. In addition, in the inoculated kimchi, the content decreased while the expression level was almost constant. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01627-8.

Synthetic, marine, light-driven, autotroph-heterotroph co-culture system for sustainable ß-caryophyllene production.

Applying low-cost substrate is critical for sustainable bioproduction. Co-culture of phototrophic and heterotrophic microorganisms can be a promising solution as they can use CO2 and light as feedstock. This study aimed to create a light-driven consortium using a marine cyanobacterium Synechococcus sp. PCC 7002 and an industrial yeast Yarrowia lipolytica. First, the cyanobacterium was engineered to accumulate and secrete sucrose by regulating the expression of genes involved in sucrose biosynthesis and transport, resulting in 4.0 g/L of sucrose secretion. Then, Yarrowia lipolytica was engineered to efficiently use sucrose and produce ß-caryophyllene that has various industrial applications. Then, co- and sequential-culture were optimized with different induction conditions and media compositions. A maximum ß-caryophyllene yield of 14.1 mg/L was obtained from the co-culture. This study successfully established an artificial light-driven consortium based on a marine cyanobacterium and Y. lipolytica, and provides a foundation for sustainable bioproduction from CO2 and light through co-culture systems.

Roseburia intestinalis-derived extracellular vesicles ameliorate colitis by modulating intestinal barrier, microbiome, and inflammatory responses.

Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent gastrointestinal inflammation, lacking a precise aetiology and definitive cure. The gut microbiome is vital in preventing and treating IBD due to its various physiological functions. In the interplay between the gut microbiome and human health, extracellular vesicles secreted by gut bacteria (BEVs) are key mediators. Herein, we explore the role of Roseburia intestinalis (R)-derived EVs (R-EVs) as potent anti-inflammatory mediators in treating dextran sulfate sodium-induced colitis. R was selected as an optimal BEV producer for IBD treatment through ANCOM analysis. R-EVs with a 76 nm diameter were isolated from R using a tangential flow filtration system. Orally administered R-EVs effectively accumulated in inflamed colonic tissues and increased the abundance of Bifidobacterium on microbial changes, inhibiting colonic inflammation and prompting intestinal recovery. Due to the presence of Ile-Pro-Ile in the vesicular structure, R-EVs reduced the DPP4 activity in inflamed colonic tissue and increased the active GLP-1, thereby downregulating the NFκB and STAT3 via the PI3K pathway. Our results shed light on the impact of BEVs on intestinal recovery and gut microbiome alteration in treating IBD.

Safety and risk factors for bleeding complications of radial probe endobronchial ultrasound-guided transbronchial biopsy.

BACKGROUND: Radial probe endobronchial ultrasound (radial EBUS) is widely used to diagnose pulmonary lesions; however, the diagnostic value of radial EBUS-guided transbronchial biopsy (TBB) varies, and its complications (especially the risk of bleeding) are not properly understood. OBJECTIVES: In this study, we evaluated the diagnostic performance and rate of complication of this procedure, and investigated the risk factors associated with the procedure-related bleeding events. DESIGN: A retrospective cohort study. METHODS: This was a retrospective study that included consecutive patients who underwent radial EBUS-guided TBB. Radial EBUS was performed under moderate sedation in inpatients or outpatients. The severity of bleeding was graded using the standardized definitions of bleeding. RESULTS: Of 133 patients (median age, 69 years; men 57.1%) included, 41 were outpatients (30.8%). The diagnostic accuracy, sensitivity, and specificity for malignancy were 76.1% (89/117), 71.1% (69/97), and 100% (20/20), respectively. The diagnostic accuracy ranged from 66.9% to 79.0%, depending on the classification of undiagnosed cases as either false negatives or true negatives. Twenty-seven patients (20.3%) developed complications (pneumothorax, 3; pneumonia, 5; complicated pleural effusion, 2; bleeding event grade 2 or higher, 21). Of the 41 outpatients, two developed complications (pneumothorax without intervention, 1; grade 2 bleeding event, 1). Of the 21 patients (15.8%) with procedure-related bleeding events, 18 had grade 2, and three had grade 3 bleeding complications. In multivariate analysis, a large size of ⩾30 mm (adjusted odds ratio (OR), 5.09; p = 0.03) and central lesion (adjusted OR, 3.67; p = 0.03) were significantly associated with the risk of grade 2 or higher bleeding events. CONCLUSION: Our results suggest that radial EBUS-guided TBB is an accurate and safe method for diagnosing pulmonary lesions. Clinically significant procedure-related bleeding was rare. The central location and larger size (⩾30 mm) of pulmonary lesions were risk factors for grade 2 or higher bleeding events.

Prospects and challenges of nanopesticides in advancing pest management for sustainable agricultural and environmental service.

The expanding global population and the use of conventional agrochemical pesticides have led to the loss of crop yield and food shortages. Excessive pesticide used in agriculture risks life forms by contaminating soil and water resources, necessitating the use of nano agrochemicals. This article focuses on synthesis moiety and use of nanopesticides for enhanced stability, controlled release mechanisms, improved efficacy, and reduced pesticide residue levels. The current literature survey offered regulatory frameworks for commercial deployment of nanopesticides and evaluated societal and environmental impacts. Various physicochemical and biological processes, especially microorganisms and advanced oxidation techniques are important in treating pesticide residues through degradation mechanisms. Agricultural waste could be converted into nanofibers for sustainable composites production, new nanocatalysts, such as N-doped TiO2 and bimetallic nanoparticles for advancing pesticide degradation. Microbial and enzyme methods have been listed as emerging nanobiotechnology tools in achieving a significant reduction of chlorpyrifos and dimethomorph for the management of pesticide residues in agriculture. Moreover, cutting-edge biotechnological alternatives to conventional pesticides are advocated for promoting a transition towards more sustainable pest control methodologies. Application of nanopesticides could be critical in addressing environmental concern due to its increased mobility, prolonged persistence and ecosystem toxicity. Green synthesis of nanopesticides offers solutions to environmental risks associated and using genetic engineering techniques may induce pest and disease resistance for agricultural sustainability. Production of nanopesticides from biological sources is necessary to develop and implement comprehensive strategies to uphold agricultural productivity while safeguarding environmental integrity.

Comparison of surgical outcomes of macular telangiectasia type 2 associated macular hole with idiopathic macular hole: A tertiary center review.

PURPOSE: To assess the longitudinal surgical outcomes of macular telangiectasia type 2 macular hole (MacTel-MH) and compare them with those of idiopathic MH. METHODS: This retrospective, single-tertiary center study included patients who underwent MH surgery between January 2015 and September 2023. Patients with characteristic optical coherence tomography (OCT) findings of MacTel in both eyes or those who underwent fluorescence angiography were classified as having MacTel MH. Baseline and postoperative best-corrected visual acuity and OCT parameters were reviewed. RESULTS: Totally, 27 and 243 eyes with MacTel and idiopathic MH, respectively, were included. MH closure rate was better achieved in idiopathic than in MacTel MH group at 2 years postoperatively. Temporal recovery of ellipsoid zone and external limiting membrane was more prominent in MacTel than in idiopathic MH group. Statistically significant visual acuity improvement was seen between 3 months and 2 years postoperatively in MacTel MH group. CONCLUSION: To the best of our knowledge, this is the first study to analyze the surgical outcomes of MacTel MH in both anatomical and functional aspects and compare them with patients with idiopathic MH. Postoperative microglia change would have affected the restoration of outer retinal layer of patients; however, further studies are needed for clarification.

Complete genome sequence of a new virus, a tentative member of the family Geminiviridae, infecting hedge bindweed (Calystegia sepium) in South Korea.

The family Convolvulaceae comprises approximately 50-60 genera with approximately 1600-1700 species, exhibiting a rich diversity of morphological characteristics and occupying a broad range of ecological habitats. High-throughput sequencing identified a tentative new virus in the family Geminiviridae infecting Calystegia sepium var. japonica in South Korea. The 2,706 nt long genome comprises six open reading frames (ORFs). The analysis of the nucleotide sequence of the genome and the putative amino acid sequences of ORFs indicated that the virus was closely related to the members of the family Geminiviridae. The genome organization of the virus was similar to that of members of the genus Topilevirus in terms of the number of ORFs and splicing signal. However, the virus, tentatively named bindweed mottle virus (BWMV), may not be assigned to current genera into the family Geminiviridae.

Incidence and Characteristics of Intraocular Lens Dislocation in South Korea from 2002 to 2021: A Nationwide Population-based Study.

Purpose: This study aimed to analyze the incidence and characteristics of intraocular lens (IOL) dislocation after cataract surgery in South Korea. Methods: We retrospectively analyzed the incidence of IOL dislocation after cataract surgery in patients diagnosed between 2002 and 2021. Data of all pseudophakic patients who underwent secondary IOL or IOL exchange surgeries due to IOL dislocation were extracted from the Korean National Health Insurance System (KNHIS) database and the Korean Standard Classification of Diseases-7 codes. The incidence per 1,000,000 person-years and corresponding 95% confidence intervals (CIs) were calculated. Results: Between 2002 and 2021, 39,965 (0.82 %) of the 4,848,125 pseudophakic patients were diagnosed with IOL dislocation and surgically treated. The incidence of IOL dislocation requiring surgery in pseudophakic patients was 28,900/1,000,000 person-years (95% CI: 28,431-29,369), comprising 57,800 cases in male and 10,800 in female patients (95% CI: male: 56,730-58,870 vs. 95% CI: female patients: 10,523-11,077), and mean male-to-female ratio was 5.35. The incidence rate peaked in younger age group below 40 years, showing 107,000 per 1,000,000 person-years (95% CI: 102,900-111,100), and the average age of IOL dislocation requiring surgery was 68.1 ± 10.7 years. The average time lapse from cataract surgery to secondary IOL surgery due to IOL dislocation was 4.1±4.7 years (median, 2.2 years), and the number of secondary IOL surgery due to dislocation of artificial lens rapidly occurred 10 years after cataract surgery among all age groups. Conclusions: The incidence of IOL dislocation requiring surgery was higher in younger and male patients. Our findings could be expected to aid establishing future healthcare policies for South Korean populations with an increased risk of IOL dislocation after cataract surgery.

Mitofusin 1 and 2 overexpression reduces AßO-mediated ER stress and apoptosis in N2a APPswe cells.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, and amyloid beta oligomers (AßO), which are pathological markers of AD, are known to be highly toxic. AßO increase mitochondrial dysfunction, which is accompanied by a decrease in mitochondrial fusion. Although mitofusin (Mfn) 1 and Mfn2 are mitochondrial fusion proteins, Mfn2 is known to regulate endoplasmic reticulum (ER) function, as it is located in the ER. Several studies have shown that AßO exacerbates ER stress, however, the exact mechanism requires further elucidation. In this study, we used mouse neuroblastoma cells stably overexpressing the amyloid precursor protein (APP) with the Swedish mutation (N2a APPswe cells) to investigate the role of Mfn in ER stress. Our results revealed that  amyloid beta (Aß) caused cellular toxicity in N2a APPswe cells, upregulated ER stress-related proteins, and promoted ER expansion. The AßO-mediated ER stress was reduced when Mfn1 and Mfn2 were overexpressed. Moreover, Mfn1 and Mfn2 overexpressed resulted in reduced apoptosis of N2a APPswe cells. In conclusion, our results indicate that both Mfn1 and Mfn2 reduce ER stress and apoptosis. Our data provide a foundation for future studies on the roles of Mfn1 and Mfn2 in the molecular mechanisms underlying AßO-mediated ER stress and the pathogenesis of AD.

Transcriptomic profiling of intermediate cell carcinoma of the liver.

BACKGROUND: Intermediate cell carcinoma (Int-CA) is a rare and enigmatic primary liver cancer characterized by uniform tumor cells exhibiting mixed features of both HCC and intrahepatic cholangiocarcinoma. Despite the unique pathological features of int-CA, its molecular characteristics remain unclear yet. METHODS: RNA sequencing and whole genome sequencing profiling were performed on int-CA tumors and compared with those of HCC and intrahepatic cholangiocarcinoma. RESULTS: Int-CAs unveiled a distinct and intermediate transcriptomic feature that is strikingly different from both HCC and intrahepatic cholangiocarcinoma. The marked abundance of splicing events leading to intron retention emerged as a signature feature of int-CA, along with a prominent expression of Notch signaling. Further exploration revealed that METTL16 was suppressed within int-CA, showing a DNA copy number-dependent transcriptional deregulation. Notably, experimental investigations confirmed that METTL16 suppression facilitated invasive tumor characteristics through the activation of the Notch signaling cascade. CONCLUSIONS: Our results provide a molecular landscape of int-CA featured by METTL16 suppression and frequent intron retention events, which may play pivotal roles in the acquisition of the aggressive phenotype of Int-CA.

Probiotic and immunostimulating effects of live and heat-killed Pediococcus pentosaceus TAP041.

The selected strain, TAP041, showing an excellent ability to reduce the glyoxal and methylglyoxal levels, was identified by 16S rRNA gene-based phylogenetic analysis as Pediococcus pentosaceus. It demonstrated probiotic properties, including acid, bile salt, pancreatin, lysozyme tolerance, gut adhesion, and auto/coaggregation. In RAW264.7 macrophages, both live and heat-killed strains induced nitric oxide production and activated inducible nitric oxide synthase. RAW264.7 treated with P. pentosaceus TAP041 increased the expression level of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and cyclooxygenase-2, and regulated the expression of c-Jun amino-terminal kinase, p38, and extracellular signal-regulated kinase. These findings suggest that both live and heat-killed P. pentosaceus TAP041 can be used as potential immunostimulatory agents in functional food additives. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01530-2.

Acid tolerance responses and their mechanisms in Lactiplantibacillus plantarum LM1001.

This study investigated the acid tolerance responses of Lactiplantibacillus plantarum LM1001 at physiological and molecular levels. Upon exposure to low pH, L. plantarum LM1001 demonstrated increased ATPase activity and ammonia consumption, which contributed to a higher intracellular pH. Comparative analysis of cell membrane fatty acids revealed that acid-stressed cells had a significantly higher proportion of unsaturated fatty acids than those of unstressed cells. There was differential upregulation of several genes, notably those involved in alkali production (arcB, argG, and argH) and in class I and class III stress responses (clpE, clpP, hrcA, dnaK, grpE, groEL, and groES). Following 2-h exposure to pH 2.5, L. plantarum LM1001 not only exhibited enhanced survival but also showed increased auto-aggregation and improved mucin adhesion capability, albeit with a reduction in hydrophobicity. These findings indicate that acid stress induces adaptive physiological and metabolic changes in L. plantarum LM1001, enhancing its acid resistance and adherence properties. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01582-4.

Secondary Breast Burkitt Lymphoma Involving the Stomach, Ovary, Pancreas, and Bones: A Case Report.

Breast lymphomas are rare, malignant breast neoplasms with a heterogeneous pattern of clinical symptoms. Burkitt's lymphoma is a rare, highly aggressive, and rapidly growing B-cell non-Hodgkin lymphoma. We report about a 27-year-old woman diagnosed as having secondary breast Burkitt's lymphoma, probably originating from the stomach, with multiple distant metastases. Breast ultrasonography revealed multiple, variable sized, heterogeneous masses with posterior acoustic enhancement and echogenic rims. These imaging findings may sometimes overlap with those of other breast malignancies. However, unlike other breast malignancies, lymphoma can be diagnosed by biopsy and does not require surgical excision. To avoid unnecessary treatment, radiologists and clinicians should be aware of the characteristic imaging features of breast lymphomas.

Field-Assisted Efficient Capturing and Analysis of Airborne Nanoparticulate Matter Using a Multifunctional Nanoporous Membrane.

As the potential adverse health and environmental effects of nanoscale pollutants have garnered significant attention, the demand for monitoring and capturing ultrafine particulate matter has been growing. With the rise in ultrafine dust emissions, this issue has become increasingly important. However, submicron particles require advanced strategies to be captured because of their limited inertial effect. For example, electrostatic air filters have been investigated for their improved performance in the fine particle regime. On the other hand, Raman spectroscopy was proposed as a promising analytical strategy for aerosol particles because it can be used to conveniently detect analytes in a label-free manner. Thus, the synergistic integration of these strategies can open new applications for addressing environment-related challenges. This study presents a multifunctional approach for achieving both air filtration and surface-enhanced Raman scattering (SERS) for analyte identification. We propose a nanoporous membrane composed of a thin gold layer, copper, and copper oxide to provide the desired functions. The structures are produced by performing scalable electrodeposition and subsequent electron-beam evaporation, attaining an excellent filtration efficiency of 95.9% with an applied voltage of 5 kV for 300 nm KCl particles and a pressure drop of 121 Pa. Raman intensity measurements confirm that the nanodendritic surface of the membrane intensifies the Raman signals and allows for the detection of 10 µL of nanoplastic particle dispersion with a concentration of 50 µg/mL. Rhodamine 6G aerosol stream with an approximate particle deposition rate of 0.040 × 106 mm-2·min-1 is also identified in a minimum detectable time of 50 s. The membrane is shown to be recyclable owing to its structural robustness in organic solvents. In addition, the fatigue resistance of the structure is evaluated through 22,000 iterative loading cycles at a pressure of 177 kPa. No performance degradation is observed after the fatigue loading.

Masked and Inverse Dynamics Modeling for Data-Efficient Reinforcement Learning.

In pixel-based deep reinforcement learning (DRL), learning representations of states that change because of an agent's action or interaction with the environment poses a critical challenge in improving data efficiency. Recent data-efficient DRL studies have integrated DRL with self-supervised learning (SSL) and data augmentation to learn state representations from given interactions. However, some methods have difficulties in explicitly capturing evolving state representations or in selecting data augmentations for appropriate reward signals. Our goal is to explicitly learn the inherent dynamics that change with an agent's intervention and interaction with the environment. We propose masked and inverse dynamics modeling (MIND), which uses masking augmentation and fewer hyperparameters to learn agent-controllable representations in changing states. Our method is comprised of a self-supervised multitask learning that leverages a transformer architecture, which captures the spatiotemporal information underlying in the highly correlated consecutive frames. MIND uses two tasks to perform self-supervised multitask learning: masked modeling and inverse dynamics modeling. Masked modeling learns the static visual representation required for control in the state, and inverse dynamics modeling learns the rapidly evolving state representation with agent intervention. By integrating inverse dynamics modeling as a complementary component to masked modeling, our method effectively learns evolving state representations. We evaluate our method by using discrete and continuous control environments with limited interactions. MIND outperforms previous methods across benchmarks and significantly improves data efficiency. The code is available at https://github.com/dudwojae/MIND.

Association of prescription data with clinical manifestations and polygenic risk scores in patients with bipolar I disorder: An exploratory study.

BACKGROUND: We assessed the association of prescription data with clinical manifestations and polygenic risk scores (PRS) in patients with bipolar I disorder. METHODS: We enrolled 1471 individuals with BID and divided them into several groups according to treatment options and clinical manifestations. BD-PRS of each patient was calculated using the Psychiatric Genomics Consortium data. Data on single nucleotide polymorphisms, clinical manifestations, and prescriptions were extracted from BiGS. RESULTS: Chronicity, suicidality, substance misuse, mixed symptoms, and deterioration of life functioning were significantly more severe in the group that was not prescribed any mood stabilizers (MS). Chronicity, psychotic symptoms, suicidality, and deterioration of life functioning were significantly severe in the group that received two or more antipsychotics (APs). BD-PRS between the group with AP(s) only and that with other treatment options significantly differed. BD-PRS of the group with AP(s) only was significantly lower than that with other treatment options. Our linear regression results showed that high severity of particular clinical aspects, lower BD-PRS, and prescriptions with fewer MSs or more APs were independently associated with poor life functioning. LIMITATIONS: This study had a cross-sectional design, without differentiating the bipolar phase, which could influence our results. CONCLUSIONS: Poor life functioning in patients with BID was associated with a high severity of particular clinical aspects, BD-PRS, and prescriptions including fewer MSs or more APs. BD-PRS was significantly higher in the group receiving only AP(s) than that in the groups receiving other drugs.

Machine learning model for osteoporosis diagnosis based on bone turnover markers.

To assess the diagnostic utility of bone turnover markers (BTMs) and demographic variables for identifying individuals with osteoporosis. A cross-sectional study involving 280 participants was conducted. Serum BTM values were obtained from 88 patients with osteoporosis and 192 controls without osteoporosis. Six machine learning models, including extreme gradient boosting (XGBoost), light gradient boosting machine (LGBM), CatBoost, random forest, support vector machine, and k-nearest neighbors, were employed to evaluate osteoporosis diagnosis. The performance measures included the area under the receiver operating characteristic curve (AUROC), F1-score, and accuracy. After AUROC optimization, LGBM exhibited the highest AUROC of 0.706. Post F1-score optimization, LGBM's F1-score was improved from 0.50 to 0.65. Combining the top three optimized models (LGBM, XGBoost, and CatBoost) resulted in an AUROC of 0.706, an F1-score of 0.65, and an accuracy of 0.73. BTMs, along with age and sex, were found to contribute significantly to osteoporosis diagnosis. This study demonstrates the potential of machine learning models utilizing BTMs and demographic variables for diagnosing preexisting osteoporosis. The findings highlight the clinical relevance of accessible clinical data in osteoporosis assessment, providing a promising tool for early diagnosis and management.

Specific bacterial co-abundance groups are associated with inflammatory status in patients with ulcerative colitis.

BACKGROUND AND AIMS: While there is increasing interest in microbiome-directed therapies for patients with ulcerative colitis (UC), the identification of microbial targets remains elusive, underlining the need for novel approaches. METHODS: Utilizing metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease, available via the IBD Plexus Program of the Crohn's & Colitis Foundation, we used a tree-based dichotomous approach to assemble distinct clusters of species-level bacterial co-abundance groups (CAGs). We evaluated the abundance of bacterial CAGs and fungal taxa during remission (n=166) and activity (n=46). We examined if the bacterial CAGs identified in our cohorts were conserved in 2 healthy cohorts and in a Korean UC cohort. RESULTS: CAG3 and CAG8, dominated by bacteria from family Lachnospiraceae, were associated with remission. Low CAG8 and elevated Candida genus were predictive of active UC. Constituents from CAG8 were influential hub species of the remission-associated microbial UC network, including Ruminococcus gnavus, Erysipelatoclostridium ramosum, Blautia and Dorea species. These hub species interactions were preserved in 2 healthy cohorts and were partially recapitulated in a Korean UC cohort. CAG8 abundance correlated with the secondary bile acid production pathway. Bacterial CAGs did not correlate with Candida, however Bifidobacterium adolescentis and Alistipes putredinis were negatively associated with Candida. CONCLUSIONS: Lachnospiriceae-dominated bacterial CAGs were associated with remission in UC, with key bacterial interactions within the CAG also observed in 2 healthy cohorts and a Korean UC cohort. Bacterial CAG-based analyses may help to inform the design of candidate consortia for microbiome-based therapeutics.