Cation Exchange Reaction-Mediated Photothermal and Polarity-Switchable Photoelectrochemical Dual-Readout Biosensor.

Cation exchange (CE) is a burgeoning method for controlled crystal synthesis; however, its applications in bioanalysis are still in their infancy. Herein, we explored the transformation of ZnIn2S4 in properties after the CE reaction with Cu2+ ions; furthermore, the discrepancy was employed to design a dual-readout detection system of photothermal and polarity-switchable photoelectrochemical (PEC) immunoassays to realize reliable detection of carcinoembryonic antigen (CEA). In the presence of CEA, the CuO nanoparticles (CuO NPs) employed as dual-signal response probes would bond to the microplates and be acidolyzed by HCl to release Cu2+, which could replace Zn2+ and In3+ via the CE reaction. After the CE reaction is completed, the photocurrent would switch from a weak anodic photocurrent to a cathode one by using a 635 nm laser as a signal amplifier, while the photothermal signal would be enhanced with 808 nm laser illumination. On the basis of the polarity-switchable PEC strategy, CEA could be accurately detected from 0.1 to 50 ng mL-1 with a limit of detection (LOD) of 48 pg mL-1 (S/N = 3). Moreover, the photothermal assay for CEA detection possesses a linear range from 0.5 to 100 ng mL-1 with a LOD of 0.21 ng mL-1. In addition, the designed sensing platform only relies on devices with portability that are permitted for point-of-care detection.

Budesonide, an anti-inflammatory drug, exacerbate clostridioides difficile colitis in mice.

BACKGROUND AND AIMS: Clostridioides difficile infection (CDI) induces intense acute inflammatory responses through toxin release. A combination of antibiotic and anti-inflammatory agents is sometimes recommended in severe, non-responsive cases, although clinical trials have been inconclusive, raising concerns about potential complications. This study aims to investigate the effect of budesonide and mesalamine in the treatment of CDI in a murine model, by evaluating the combination of fidaxomicin and these anti-inflammatory drugs. METHOD: C57BL/6 J female mice pretreated with an antimicrobial mixture were challenged with C. difficile VPI 10463 or culture media by gavage. After the challenge, mice received placebo, fidaxomicin alone (20 mg/kg), or fidaxomicin combined with mesalamine (200, 400 mg/kg) or budesonide (0.2, 1, 10 mg/kg) for 5 days. The mice were monitored for 7 days with weight and survival. Colon and cecum tissues were harvested for histological assessment. RESULTS: CDI of mice caused 80% mortality. Fidaxomicin completely protected against CDI in all parameters (weight, survival and pathscores). Mortality rates were up to 90%, 70% in budesonide(10 mg/kg) and mesalamine (400 mg/kg) treatment group, respectively. Budesonide (0.02,0.1 and 1 mg/kg) adjunction to fidaxomicin worsened the disease outcome according to all tested parameters. While mesalamine in combination with fidaxomicin (200, 400 mg/kg) did not lead to any deaths during CDI treatment, it did not provide additional benefits. CONCLUSIONS: Anti-inflammatory drugs including corticosteroid therapy may worsen the incidence and severity of CDI in this mouse model. These studies may have important clinical implications for understanding the role of anti-inflammatory/ corticosteroid therapy in CDI and inflammatory bowel disease management.

Linked mutations within the pathogenicity locus of Clostridioides difficile increase virulence.

BACKGROUND: The clinical manifestations of Clostridioides difficile infections range from diarrhoea to pseudomembranous colitis (PMC) and death. We evaluated the association between gene content in C. difficile clinical isolates and disease severity. METHODS: Fifty-three C. difficile isolates were subjected to Sanger sequencing, clinical data were used to analyse the association of gene content with disease severity, and 83 non-duplicate isolates were collected to confirm the results. Virulence was further examined by functional in vitro and in vivo experiments. RESULTS: Among the 53 C. difficile isolates, ribotypes 017 (n = 9, 17.0%) and 012 (n = 8, 15.1%) were predominant. Fifteen strains exhibited a correlation between mutations of pathogenicity locus genes (tcdB, tcdC, tcdR, and tcdE) and were named linked-mutation strains. Ribotypes are not associated with clinical PMC and Linked-mutation strains. The proportion of patients with PMC was higher in the group infected with linked-mutation strains than in the non-linked-mutation group (57.14% vs. 0%, p < 0.001). The linked-mutation rate of C. difficile was higher in patients with PMC than in patients without PMC (89.47% vs. 7.8%, p < 0.0001). Linked-mutation strains showed greater cytotoxicity in vitro and caused more severe tissue damage in a mouse model. CONCLUSIONS: Linked-mutation strains are associated with high virulence and PMC development. This result will help monitor the clinical prognosis of C. difficile infection and provide key insights for developing therapeutic targets and monoclonal antibodies.

Self-assembled p-n Ag2O@Bi2O2S nanoflower heterojunctions for sensitive photoelectrochemical immunoassay.

A new photoelectrochemical immunoassay based on self-assembled p-n Ag2O@Bi2O2S nanoflower heterojunction was designed and developed for quantitative monitoring of prostate-specific antigen (PSA) in biological fluids. Primarily, self-assembled p-n Ag2O@Bi2O2S nanoflower heterojunctions were served as the photoactive materials and coated onto the surface of electrodes. Subsequently, the glucose oxidase (GOx) was bound to the detection antibody (mAb2) labeled gold nanoparticles (Au NPs) and then were employed to accomplish a sandwich-like immunoreaction to generate H2O2 on a microplate incubated with monoclonal anti-PSA antibodies. In the presence of PSA, the product (H2O2) was catalyzed by the substrate, which was used as an electron sacrificial agent to improve signal conversion and capture of photogenerated electrons. Under optimum conditions, a wide linear range of 0.01-50 ng mL-1 and a low detection limit of 5.3 pg mL-1 were accomplished with the sensor, exhibiting an excellent photocurrent response. Moreover, the proposed sensor revealed satisfactory reproducibility, high selectivity, and acceptable accuracy for the real sample testing. Importantly, our work provides a novel strategy for high sensitivity detection of disease-associated biomarkers for the early diagnosis of cancers.

Inflammatory bowel disease is causally related to irritable bowel syndrome: a bidirectional two-sample Mendelian randomization study.

Introduction: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are lifelong digestive diseases that severely impact patients' quality of life. The existence of a causal association between IBS and IBD remains unclear. This study aimed to determine the direction of causality between IBD and IBS by quantifying their genome-wide genetic associations and performing bidirectional two-sample Mendelian randomization (MR) analyses. Methods: Genome-wide association studies (GWAS) among a predominantly European patient cohort identified independent genetic variants associated with IBS and IBD. Two separate databases (a large GWAS meta-analysis and the FinnGen cohort) for both IBS and IBD were consulted to retrieve statistics on instrument-outcome associations. MR analyses included inverse-variance-weighted, weighted-median, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods, and sensitivity analyses were performed. The MR analyses were carried out for each outcome data, followed by a fixed-effect meta-analysis. Results: Genetically predicted IBD was associated with an increased risk of IBS. Odds ratios (95% confidence intervals) for samples of 211,551 (17,302 individuals with IBD), 192,789 (7,476 Crohn's disease cases), and 201,143 (10,293 ulcerative colitis cases) individuals were 1.20 (1.00, 1.04), 1.02 (1.01, 1.03), and 1.01 (0.99, 1.03), respectively. After outlier correction using MR-PRESSO, the odds ratio for ulcerative colitis was 1.03 (1.02, 1.05) (p = 0.001). However, an association between genetically influenced IBS and IBD was not identified. Discussion: This study confirms that IBD is causally related to IBS, which may interfere with the diagnosis and treatment of both diseases.

Ag/MoO3-Pd-mediated gasochromic reaction: An efficient dual-mode photoelectrochemical and photothermal immunoassay.

Herein, we presented a dual-readout gasochromic immunosensing platform for accurate and sensitive detection of carcinoembryonic antigen (CEA) based on Ag-doped/Pd nanoparticles loaded MoO3 nanorods (Ag/MoO3-Pd). Initially, the presence of analyte CEA would prompt the formation of sandwich-type immunoreaction, accompanied by the introduction of Pt NPs labeled on detection antibody. Upon the addition of NH3BH3, the product hydrogen (H2) will interact with Ag/MoO3-Pd as a bridge between the sensing interface and the biological assembly platform. Both photocurrent and temperature signals can serve as readouts due to the significantly increased PEC performance and enhanced photothermal conversion capability of H-Ag/MoO3-Pd (the product of Ag/MoO3-Pd react with H2) compared to Ag/MoO3-Pd. In addition, the DFT results show that the band gap of Ag/MoO3-Pd becomes narrower after the reaction with H2, thus improving the utilization of light, which theoretically explains the internal mechanism of gas sensing reaction. Under optimal conditions, the designed immunosensing platform showed good sensitivity for CEA detection with the limit of detection (LOD) of 26 pg mL-1 (photoelectrochemical mode) and 98 pg mL-1 (photothermal mode). This work not only presents the possible reaction mechanism of Ag/MoO3-Pd and H2, but also creatively applicate it in photothermal biosensors that give a new path for devising dual-readout immunosensor.

Bio-inspired nanozyme with ultra-thin Fe-Bi2O2S nanosheets for in-situ amplified photoelectrochemical immunoassay of cancer-related protein.

A Fe-loaded Bi2O2S nanosheet photoanode serving as photoelectric biomonitoring platform for the detection of prostate-specific antigen (PSA) using biologically inspired prussian nanoparticle (PB)-catalyzed biocatalytic precipitation strategy was developed. Primarily, the signal probe PB-mAb2 obtained by electrostatic adsorption was immobilized on a microplate in the presence of target PSA, and 4-chloro-1-naphthol (4-CN) was oxidized to benzo-4-chloro-hexadienone (4-CD) with the assistance of exogenous hydrogen peroxide, which was generated by a large number of hydroxyl radicals catalyzed by PB. The generated 4-CD showed strongly low conductivity characteristics to burst the photocurrent of highly photoactive Fe-Bi2O2S photoanode. The split incubation reaction could be suitable for high volume and low-cost rapid detection. A dynamic response range of 0.1-100 ng mL-1 with a limit of detection of 34.2 pg mL-1 was achieved with the sensor based on a photoelectric sensing platform and a biomimetic catalytic precipitation reaction. Equally important, the sensor also showed good potential in the detection of real samples compared to commercially available ELISA kits. In conclusion, this work provides a fresh scheme for the development of sensitive biosensors through a bio-inspired catalytic strategy of versatility and a photoanode coupling with high photoelectric activity.

Smartphone-based photoelectrochemical immunoassay of prostate-specific antigen based on Co-doped Bi2O2S nanosheets.

Portable and on-site detection of target biomarker is of great significance in early diagnosis of diseases. Herein, we designed a portable smartphone-based PEC immunoassay platform to detect prostate specific antigen (PSA) adopting Co-doped Bi2O2S nanosheets as photoactive materials. The fast photocurrent response under visible light and excellent electrical transport rate invest Co-doped Bi2O2S with the property of being effectively excited even under a weak light source. Therefore, with the incorporation of a carriable flashlight that act as the excitation light source, disposable screen-printed electrodes, a microelectrochemical workstation and a smartphone that served as control center, point-of-care analytical detection of low-abundance small molecule analytes was successfully realized. Specifically, a sandwich-type immunoreaction was performed using alkaline phosphatase labeled secondary antibody as signal indicator. In the presence of PSA, ascorbic acid as generated through a catalytic reaction, resulting in the enhancement of photocurrent intensity. The photocurrent intensity increased linearly with the logarithm of PSA concentrations ranging from 0.2 to 50 ng mL-1 with a detection limit of 71.2 pg mL-1 (S/N = 3). This system provided an effective method for the construction of portable and miniaturized PEC sensing platform for the application of point-of-care health monitoring.

Preservation of the Innate Immune Response to Clostridioides difficile Infection in Hospitalized Immunocompromised Patients.

Background: Clostridioides difficile infection (CDI) immune response is influenced by the innate and adaptive (humoral) immune systems. Our prior research found attenuated humoral responses to C difficile in immunocompromised hosts (ICHs) with CDI. We sought to evaluate whether the innate immune response to CDI was influenced by ICH status. Methods: We conducted a prospective study of hospitalized adults with CDI (acute diarrhea, positive C difficile stool nucleic acid amplification testing [NAAT], and decision to treat), with and without immunosuppression and measured a panel of cytokines (granulocyte colony-stimulating factor [G-CSF], interleukin [IL]-10, IL-15, IL-1ß, IL-4, IL-6, IL-8, and tumor necrosis factor-α) in blood and stool at CDI diagnosis. Results were compared with measurements from a cohort of asymptomatic carrier patients (ASCs) (NAAT positive, without diarrhea) with and without immunocompromise. Results: One hundred twenty-three subjects (42 ICHs, 50 non-ICHs, 31 ASCs) were included. Median values for blood and stool cytokines were similar in ICH versus non-ICH CDI subjects. In blood, G-CSF, IL-10, IL-15, IL-6, and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P < .05). In stool, IL-1ß and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P < .05). Median stool concentrations of IL-1ß demonstrated significant differences between the groups (ICHs, 10.97 pg/mL; non-ICHs, 9.71 pg/mL; and ASCs, 0.56 pg/mL) (P < .0001). Conclusions: In this small exploratory analysis, ICH status did not significantly impact blood and fecal patterns of cytokines in humans at the diagnosis of CDI, suggesting that the innate immune response to C difficile may be conserved in immunocompromised patients.

A nomogram and risk classification system predicting esophageal stricture after endoscopic submucosal dissection of a large area for early esophageal cancer.

BACKGROUND AND OBJECTIVES: Esophageal stricture is a troublesome adverse effect of endoscopic submucosal dissection (ESD) for early esophageal cancer. However, risk factors of post-ESD esophageal stricture formation are incomprehensive. This study aimed to conduct a comprehensive analysis of independent risk factors and provide predictive tools. METHODS: Patients who underwent ESD for early esophageal cancer between 2014 and 2021 at the Beijing Friendship Hospital, Capital Medical University, were recruited. A nomogram and risk classification system was established based on Cox proportional hazards analyses and validated using the concordance index (C-index), calibration curves, decision curve analysis (DCA), and Kaplan-Meier (K-M) curves. RESULTS: Stricture formed in 36 patients, while stricture was not observed in the remaining 112 patients. Operative time (odds ratio [OR]: 1.01; 95% confidence interval [CI]: 1.00-1.01; p < 0.01); lesions >3/4 circumferential range of esophagus (OR: 3.82; 95% CI: 1.90-7.66; p < 0.01), and tumor infiltration to the mucosal lamina propria (m2) or deeper (OR: 2.40; 95% CI: 1.24-4.66; p = 0.01) were independent predictive factors for post-ESD esophageal stricture. The nomogram and risk classification system was developed and validated with 0.79 C-index, good calibration curves, good DCA results, and good K-M curves. CONCLUSIONS: We developed a nomogram and risk stratification system to predict post-ESD esophageal stricture using three independent risk factors.

Integrated solar-powered MEMS-based photoelectrochemical immunoassay for point-of-care testing of cTnI protein.

Considering the fact that acute myocardial infarction has shown a trend towards younger age and has become a major health problem, it is necessary to develop rapid screening devices to meet the needs of community health care. Herein, we developed an artificial neural network-assisted solar-powered photoelectrochemical (SP-PEC) sensing platform for rapid screening of cardiac troponin I (cTnI) protein in the prognosis of patients with acute myocardial infarction (AMI) by integrating a self-powered photoelectric signal output system with low-cost screen-printed paper electrodes functionalized with ultrathin Bi2O2S (BOS) nanosheets. An integrated solar-powered PEC immunoassay with micro-electro-mechanical system (MEMS) was constructed without an excitation light source. The quantification of cTnI protein was obtained by the electrical signal changes caused by the electro-oxidation process of H2O2, generated by the classical split immune reaction, on the electrode surface. The test electrodes were developed as dual working electrodes, one for target cTnI testing and the other for evaluating light intensity, to reduce the temporal inconsistency of sunlight. The photoelectrodes were discovered to exhibit satisfactory negative response to target concentrations in the dynamic range of 2.0 pg mL-1-10 ng mL-1 since being regressed in an improved artificial neural network (ANN) model using the pooled dataset of target signals affected by the light source. The difference of hot electron and hole transfer behavior in different thickness of nano-materials was determined by finite element analysis (FEA), which provided a theoretical basis for the development of efficient PEC sensors. This work presents a unique perspective for the design of a revolutionary low-cost bioassay platform by inventively illuminating the PEC biosensor's component process without the use of light.

Global trends in Akkermansia muciniphila research: A bibliometric visualization.

Background: Akkermansia muciniphila is a member of the gut microbiome, using mucin as sources of carbon, nitrogen, and energy. Since the first discovery of this unique bacterium in 2004, A. muciniphila has been extensively studied. It is considered a promising "next-generation beneficial microbe." The purpose of this paper is to sort out the research status and summarize the hotspots through bibliometric analysis of the publications of A. muciniphila. Methods: The publications about A. muciniphila from January 2004 to February 2022 were obtained from the Web of Science Core Collection. Visualization analyses were performed using three bibliometric tools and GraphPad Prism. Results: A total of 1,478 published documents were analyzed. Annual publication number grew from 1 in 2004 to 336 in 2021, with China being the leading producer (33.36%). De Vos, Willem M was the most productive author with the highest H-index (documents = 56, H-index = 37), followed by Cani, Patrice D (documents = 35, H-index = 25). And Scientific Reports published the most papers. PNAS was the keystone taxa in this field, with high betweenness centrality (0.11) and high frequency. The keywords with high frequency in recent years include: oxidative stress, diet, metformin, fecal microbiota transplantation, short-chain fatty acids, polyphenols, microbiota metabolites and so on. The keyword "oxidative stress" was observed to be increasing in frequency recently. Conclusion: Over time, the scope of the research on the clinical uses of A. muciniphila has gradually increased, and was gradually deepened and developed toward a more precise level. A. muciniphila is likely to remain a research hotspot in the foreseeable future and may contribute to human health.

Dual-mode colorimetric-photothermal sensing platform of acetylcholinesterase activity based on the peroxidase-like activity of Fe-N-C nanozyme.

Sensors based on colorimetry, fluorescence, and electrochemistry have been widely employed to detect acetylcholinesterase and its inhibitors, however, there are only a minority of strategies for AChE detection based on photothermal method. This work reports a versatile dual-mode colorimetric and photothermal biosensing platform for acetylcholinesterase (AChE) detection and its inhibitor (paraoxon-ethyl, a model of AChE inhibitors) monitor based on Fe-N-C/H2O2/3,3',5,5'-tetramethylbenzidine (TMB) system. The Fe-N-C with abundant active Fe-Nx sites shows outstanding peroxidase-mimicking activity and can be used to promote the generation of •OH by H2O2 to oxidize TMB. However, the introduction of mercapto molecules tending to coordinate with metal atoms result in the block of action site in Fe-N-C, thereby decrease its peroxidase-mimetic activity. The designed biosensor principle is based on the block of active sites of Fe-N-C by thiocholine (TCh, one kind of mercapto molecules) that can be produced by acetylthiocholine (ATCh) in the presence of AChE. Under optimum conditions, the limit of detection (LOD) for AChE activity is 1.9 mU mL-1 (colorimetric) and 2.2 mU mL-1 (photothermal), while for paraoxon-ethyl is 0.012 µg mL-1 (colorimetric) and 0.013 µg mL-1 (photothermal), respectively. The assay we proposed not only can be designed to monitor AChE detection and its inhibitors, but also can be easily extended for the detection of other biomolecules relate to the generation or consumption of H2O2.

Snowflake-like CdS@ZnIn2S4 heterojunction-based photocatalyst-electrolyte effect: An innovative mode for photoelectrochemical immunoassay.

Exploiting innovative strategies with signal amplification in photoelectrochemical (PEC) biosensing systems to realize sensitive screening of low-abundance proteins has become one of the mainstream research orientations. Herein we reported a new strategy to amplify photocurrent signal employing a photocatalyst-electrolyte effect in alkaline media for the sensitive monitoring of prostate-specific antigen (PSA) using snowflake-liked CdS@ZnIn2S4 heterojunction as photosensitizer. In this strategy, both the band-edge position and surface redox reaction process were subtly altered by modulating the alkalinity of electrolyte. The hydroxyl anions (OH-) from NaOH could be oxidized to hydroxyl radicals (·OH) by the holes in CdS@ZnIn2S4, thus accelerating the scavenging of holes and promoting the photocurrent. Based on the above-mentioned mechanism, a sensitive split-type glucose oxidase-mediated PEC immunosensor for PSA detection was fabricated. Upon target PSA introduction, the glucose acid was generated through the sandwich-type immunoreaction to affect the alkalinity of PEC detection environment, thereby suppressing the photocurrent intensity. The CdS@ZnIn2S4-based PEC immunosensor exhibited satisfactory photocurrent responses with a good linear range of 0.04-40 ng mL-1 at a limit of detection of 14 pg mL-1. Significantly, this research not only introduces an effective strategy to detect PSA with good sensitivity and specificity, but also provides a new insight to amplify the signal by regulating the electrolyte.

In2O3/CdIn2S4 heterojunction-based photoelectrochemical immunoassay of carcinoembryonic antigen with enzymatic biocatalytic precipitation for signal amplification.

This work reported a split-type photoelectrochemical (PEC) immunoassay for the detection of carcinoembryonic antigen (CEA) based on target-induced biocatalytic precipitation (BCP) by using In2O3/CdIn2S4 heterojunctions as the photosensitizers. The synthesized In2O3/CdIn2S4 heterojunctions improved the efficiency of charge separation and shortened the electron convey path to enhance the photocurrent, thus exhibiting high conductivity and low complexation rates of photogenerated electrons and holes. In the presence of CEA, horseradish peroxidase (HRP) catalyzed 4-chloro-1-naphthol (4-CN) to produce benzo-4-chloro-hexadienone (4-CD) through H2O2. Then, 4-CD was deposited onto the surface of In2O3/CdIn2S4 to reduce the photocurrent and realized the signal amplification. The PEC immunoassay revealed an excellent photocurrent toward target CEA within a wide range of 0.01-50 ng mL-1 at a low limit of detection of 2.8 pg mL-1 under the optimum conditions. Multiple switching light excitation tests demonstrated the good reliability and stability of the fabricated PEC biosensor. The accuracy was acceptable in comparison with human CEA enzyme-linked immunosorbent assay (ELISA) kit.

Development and clinical application of a rapid and visual loop-mediated isothermal amplification test for tetM gene in Clostridioides difficile strains cultured from feces.

OBJECTIVES: In this study, we aimed to develop a rapid and visual loop-mediated isothermal amplification (LAMP) assay targeting the tetM gene in Clostridioides difficile strains cultured from feces. METHODS: Primers were designed to recognize the tetM gene in C. difficile by LAMP, using turbidity and visual detection. The sensitivity and specificity of LAMP primers were determined. In addition, we conducted both LAMP and polymerase chain reaction (PCR) for the tcdA, tcdB, cdtA, cdtB, ermB, and tetM genes in 300 toxigenic C. difficile strains cultured from feces. RESULTS: The target DNA was amplified and visualized within 60 minutes at a temperature of 62°C. A total of 26 bacterial strains were found negative for tetM, which manifested high specificity of the primers. The detection limit of LAMP was 36.1 pg/µl, which was 100-fold more sensitive than PCR. The positive rate of tetM in toxigenic C. difficile strains cultured from feces was 93.3% by both LAMP and PCR. The proportion of toxin types in those C. difficile strains was 95.7% for A+B+CDT-, 4% for A-B+CDT-, and 0.3% for A+B+CDT+, respectively. CONCLUSION: This is the first study examining the tetM gene by LAMP in C. difficile strains cultured from feces. Its high specificity, sensitivity, and visual detection make the new assay a powerful diagnostic tool for rapid testing.

Photoelectrochemical bioanalysis of microRNA on yolk-in-shell Au@CdS based on the catalytic hairpin assembly-mediated CRISPR-Cas12a system.

This work reports on the proof-of-concept of a photoelectrochemical (PEC) biosensor with a horseradish peroxidase-single stranded DNA-encoded magnetic bead (MB-ssDNA-HRP) signal probe cleaved by the catalytic hairpin assembly (CHA)-mediated clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a system for the quantification of microRNA (miR-21) by using yolk-in-shell Au@CdS as a photoactive material.

Global trends in gut microbiota and clostridioides difficile infection research: A visualized study.

BACKGROUND: Clostridioides (clostridium) difficile infection (CDI) is the most common cause of nosocomial diarrheal disease, which has become a public health problem worldwide; gut dysbiosis plays a central role in its pathophysiology. This study conducted a bibliometric analysis of publications on gut microbiota and CDI to summarize the current status of research including research hotspots. METHODS: Relevant publications from January 2004 to February 2022 were identified from the Web of Science Core Collection. Three bibliometric tools were used to perform visualization analyses. RESULTS: A total of 1983 publications were analyzed. Annual publications increased from 11 in 2004-237 in 2021, with the US being the leading producer (47.55 % of all papers). EG Pamer had the highest average citations per article (average citations per item = 153.03, H-index = 29). Frontiers in Microbiology published the most papers. The main research foci were "fecal microbiota transplantation," "colonization resistance," and "multidrug-resistant bacteria." The keywords with the highest frequency in recent years include: gut dysbiosis, antibiotic resistance, bile-acids, 16 s sequencing, multidrug-resistant bacteria, and short chain fatty acids. CONCLUSIONS: Gut microbiota and CDI is likely to remain a prominent area of research in the foreseeable future. Current research hotspots ("fecal microbiota transplantation," "colonization resistance," and "multidrug-resistant bacteria") should receive even more attention in future studies.

Humoral Immune Response to Clostridioides difficile Toxins A and B in Hospitalized Immunocompromised Patients With C difficile Infection.

BACKGROUND: The humoral immune response to Clostridioides difficile toxins in C difficile infection (CDI) is incompletely characterized in immunocompromised hosts (ICHs). METHODS: We conducted a prospective study of hospitalized adults with CDI, with and without immunosuppression (hematologic malignancy, active solid tumor, solid organ or stem cell transplant, inflammatory bowel disease, autoimmune disease, congenital or acquired immunodeficiency, asplenia, chronic receipt of high-dose steroids, or receipt of immunosuppressing medications within 12 months). Serum and stool antibody concentrations of immunoglobulin (Ig)M, IgG, and IgA to C difficile toxins A and B at treatment days 0, 3, and 10-14 were compared. RESULTS: Ninety-eight subjects (47 ICH; 51 non-ICH) were enrolled. Baseline serum antitoxin A and B antibody levels were similar. At day 3, ICHs demonstrated lower serum levels of antitoxin A IgG, antitoxin A IgA, and antitoxin B IgA (all P < .05). At day 10-14, lower antitoxin A IgG concentrations were observed in ICHs (ICH, 21 enzyme-linked immunosorbent assay [ELISA] units; interquartile range [IQR], 16.4-44.6) compared with non-ICH subjects (49.0 ELISA units; IQR, 21.5-103; P = .045). In stool, we observed lower concentrations of antitoxin B IgA antibodies at baseline and at day 3 for ICH subjects, with a notable difference in concentrations of antitoxin B IgA at day 3 (ICH, 6.7 ELISA units [IQR, 1.9-13.9] compared with non-ICH, 18.1 ELISA units [IQR, 4.9-31.7]; P = .003). CONCLUSIONS: The ICHs with CDI demonstrated lower levels of C difficile antitoxin antibodies in serum and stool during early CDI therapy compared with non-ICHs. These data provide insight into the humoral response to CDI in ICHs.

Integrating gut microbiome and host immune markers to understand the pathogenesis of Clostridioides difficile infection.

Clostridioides difficile (C.difficile) infection is the most common cause of healthcare-associated infection and an important cause of morbidity and mortality among hospitalized patients. A comprehensive understanding of C.difficile infection (CDI) pathogenesis is crucial for disease diagnosis, treatment, and prevention. Here, we characterized gut microbial compositions and a broad panel of innate and adaptive immunological markers in 243 well-characterized human subjects (including 187 subjects with both microbiota and immune marker data), who were divided into four phenotype groups: CDI, Asymptomatic Carriage, Non-CDI Diarrhea, and Control. We found that the interactions between gut microbiota and host immune markers are very sensitive to the status of C.difficile colonization and infection. We demonstrated that incorporating both gut microbiome and host immune marker data into classification models can better distinguish CDI from other groups than can either type of data alone. Our classification models display robust diagnostic performance to differentiate CDI from Asymptomatic carriage (AUC~0.916), Non-CDI Diarrhea (AUC~0.917), or Non-CDI that combines all other three groups (AUC~0.929). Finally, we performed symbolic classification using selected features to derive simple mathematic formulas that explicitly quantify the interactions between the gut microbiome and host immune markers. These findings support the potential roles of gut microbiota and host immune markers in the pathogenesis of CDI. Our study provides new insights for a microbiome-immune marker-derived signature to diagnose CDI and design therapeutic strategies for CDI.