Background Clostridium difficile (C. difficile) is one of the most common hospital-acquired infections and causes the release of various cytokines. Prostate cancer (PC) is the second most com...

Whey protein (WP) and its components account for 20% of bovine milk proteins. Once considered as a waste by-product of cheese production, WP is now kn…

The incidence of CDI in the southern area of China was low. Age 60 years, and treatment in geriatric or neurosurgery units were independent risk factors for CDI inpatients.

Clostridioides difficile (C. difficile) toxins A (TcdA) and B (TcdB) cause antibiotic-associated colitis in part by disrupting epithelial barrier function. Accurate in vitro models are necessary to detect early toxicity kinetics, investigate disease etiology, and develop preclinical models for new therapies. Properties of cancer cell lines and organoids inherently limit these efforts. We developed adult stem cell-derived monolayers of differentiated human colonic epithelium (hCE) with barrier function, investigated the impact of toxins on apical/basal aspects of monolayers, and evaluated whether a leaky epithelial barrier enhances toxicity. Single-cell RNA-sequencing (scRNAseq) mapped C. difficile-relevant genes to human lineages. Transcriptomics compared hCE to Caco-2, informed timing of in vitro stem cell differentiation, and revealed transcriptional responses to TcdA. Transepithelial electrical resistance (TEER) and fluorescent permeability assays measured cytotoxicity. Contribution of TcdB toxicity was evaluated in a diclofenac-induced leaky gut model. scRNAseq demonstrated broad and variable toxin receptor expression. Absorptive colonocytes in vivo displayed increased toxin receptor, Rho GTPase, and cell junction gene expression. Advanced TcdA toxicity generally decreased cytokine/chemokine and increased tight junction and death receptor genes. Differentiated Caco-2 cells remained immature whereas hCE monolayers were similar to mature colonocytes in vivo. Basal exposure of TcdA/B caused greater toxicity and apoptosis than apical exposure. Apical exposure to toxins was enhanced by diclofenac. Apical/basal toxicities are uncoupled with more rapid onset and increased magnitude postbasal toxin exposure. Leaky junctions enhance toxicity of apical TcdB exposure. hCE monolayers represent a physiologically relevant and sensitive system to evaluate the impact of microbial toxins on gut epithelium. NEW & NOTEWORTHY Novel human colonocyte monolayer cultures, benchmarked by transcriptomics for physiological relevance, detect early cytopathic impacts of Clostridioides difficile toxins TcdA and TcdB. A fluorescent ZO-1 reporter in primary human colonocytes is used to track epithelial barrier disruption in response to TcdA. Basal TcdA/B exposure generally caused more rapid onset and cytotoxicity than apical exposure. Transcriptomics demonstrate changes in tight junction, chemokine, and cytokine receptor gene expression post-TcdA exposure. Diclofenac-induced leaky epithelium enhanced apical exposure toxicity.

Antimicrobial resistance has caused chaos worldwide due to the depiction of multidrug-resistant (MDR) infective microorganisms. A thorough examination of antimicrobial resistance (AMR) genes and associated resistant mechanisms is vital to solving this problem. Clostridium difficile (C. difficile) is …

Similarities between the symptoms of Clostridioides difficile infection and Crohn disease may cause confusion for health care providers.

Spore formation is required for environmental survival and transmission of the human enteropathogenic Clostridioides difficile . In all bacterial spore formers, sporulation is regulated through activation of the master response regulator, Spo0A. However, the factors and mechanisms that direct …

The results show similar rates o colonized C difficile among pediatric patients and adult patients with cystic fibrosis.

Patients with no prior colonoscopy had significantly higher all-cause mortality and colorectal cancer specific mortality compared to patients with detected colorectal cancer.

Scientists succeeded in defining a new algorithm to systematically profile gut microbiome metabolism, identifying 19,890 gene clusters in 4,240 high-quality microbial genomes:https://t.co/c7GNu7mtiZ— GutMicrobiota Health (@GMFHx) April 7, 2023

Clostridioides difficile infection (CDI) is the major identifiable cause of antibiotic-associated diarrhea and has been declared an urgent threat by the CDC. C. difficile forms dormant and resistant spores that serve as infectious vehicles for CDI. To cause disease, C. difficile spores recognize tau …

The majority of patients felt it was important for healthcare providers talk to them about the symptoms, possible treatments. In addition, most patients are not prescribed a medication right away.

A commensal bacterium exploits phase separation of a transcription termination factor to colonize the gut.

Clostridioides difficile remains a key cause of healthcare-associated infection, with multidrug-resistant (MDR) lineages causing high-mortality (≥20%) outbreaks. Cephalosporin treatment is a long-established risk factor, and antimicrobial stewardship is a key control. A mechanism underlying raised c …

Clostridioides difficile infection (CDI) is the major identifiable cause of antibiotic-associated diarrhea and has been declared an urgent threat by the CDC. C. difficile forms dormant and resistant spores that serve as infectious vehicles for CDI. To cause disease, C. difficile spores recognize tau …

The Journal of Antibiotics - Mechanism of germination inhibition of Clostridioides difficile spores by an aniline substituted cholate derivative (CaPA)

#Cdiff is anaerobic, gram-positive bacterium that exists in both vegetative and spore forms. #GITwitter #IDTwitter #guthealth pic.twitter.com/dShF4xROao— Microbiome Science (@MbiomeScience) April 2, 2023

Immune checkpoint inhibitors (ICI) are commonly used for various malignancies. A particular checkpoint inhibitor is the anti-PD-1 antibody pembrolizumab. Immune-mediated diarrhea and colitis (IM...

Crohn’s disease (CD) is a type of inflammatory bowel disease (IBD) characterized by chronic transmural inflammation of any portion of the gastrointestinal tract. The etiology of CD remains unkno...

Immune checkpoint inhibitors (ICI) are commonly used for various malignancies. A particular checkpoint inhibitor is the anti-PD-1 antibody pembrolizumab. Immune-mediated diarrhea and colitis (IM...

“Recent findings show infants born to mothers with IBD present with altered gut microbiome that transfers abnormalities of the adaptive immune system to germ-free mice. Learn more on this podcast with experts: https://t.co/asfeR31UEI”

Researchers have used a systems biology approach to parse the genetic diversity of Clostridioides difficile, a particularly problematic pathogen, particularly in health care settings.

Antibiotic resistance (ARE) is a threat to human health worldwide, as diverse proteins allow pathogenic bacteria to develop increasing levels of resistance to antibiotic medicines. Now, a team from the ...

Clostridioides difficile infection (CDI) remains a significant healthcare burden. Non-toxigenic C. difficile (NTCD) strains have shown a benefit in preventing porcine enteritis and in human recurrent CDI. In this study, we evaluated the efficacy of metronidazole-resistant NTCD-E4 in pr …

The main symptoms of coronavirus disease (COVID-19) are fever, cough, tiredness, and loss of smell and taste. Gastrointestinal symptoms are less common. A 38-year-old female patient, previously healthy, presented with a history of hematochezia up to 8 times per day, followed by abdominal cramps, urg …

Culture-independent metagenomic studies have revolutionized our understanding of the gut microbiota.Scientists present a substantially expanded Cultivated Genome Reference of the human gut microbiota with 179 previously unidentified species:https://t.co/teyjbpcQ8g— GutMicrobiota Health (@GMFHx) March 28, 2023

Traditional clinical models for predicting recurrent Clostridioides difficile infection do not perform well, likely owing to the complex host-pathogen interactions involved. Accurate risk stratification using novel biomarkers could help prevent recurrence by improving underutilization of effective t …

In conclusion, the CRISPR-based double toxin gene detection platform for C. difficile is an effective, specific, and sensitive detection method, which can be used as a powerful on-site detection tool for POCT in the future.

Industrialization has transformed the gut microbiota, reducing the prevalence of Prevotella relative to Bacteroides . Here, we isolate Bacteroides and Prevotella strains from the microbiota of Hadza hunter-gatherers of Tanzania, a population with high levels of Prevotella . We demonstrate that plant-derived microbiota-accessible carbohydrates (MACs) are required for persistence of Prevotella copri but not Bacteroides thetaiotaomicron in vivo . Differences in carbohydrate metabolism gene content, expression, and in vitro growth reveal that Hadza Prevotella strains specialize in degrading plant carbohydrates, while Hadza Bacteroides isolates use both plant and host-derived carbohydrates, a difference mirrored in Bacteroides from non-Hadza populations. When competing directly, P. copri requires plant-derived MACs to maintain colonization in the presence of B. thetaiotaomicron , as a no MAC diet eliminates P. copri colonization. Prevotella’s reliance on plant-derived MACs and Bacteroides’ ability to use host mucus carbohydrates could explain the reduced prevalence of Prevotella in populations consuming a low-MAC, industrialized diet. Statement on work with indigenous communities In order to acquire scientific knowledge that accurately represents all human populations, rather than only reflecting and benefiting those in industrialized nations, it is necessary to involve indigenous populations in research in a legal, ethical, and non-exploitative manner ([Abdill et al., 2022][1]; [Green et al., 2020][2]). Here, we isolated live bacterial strains from anonymized fecal samples collected from Hadza hunter-gatherers in 2013/2014 ([Fragiadakis et al., 2019][3]; [Merrill et al., 2022][4]; [Smits et al., 2017][5]). Samples were collected with permission from the Tanzanian government, National Institute of Medical Research (MR/53i 100/83, NIMR/HQ/R.8a/Vol.IX/1542), the Tanzania Commission for Science and Technology, and with aid from Tanzanian scientists. A material transfer agreement with the National Institute for Medical Research in Tanzania specifies that collected samples are solely to be used for academic purposes. For more information on the consent practices followed, and our ongoing work to communicate the results of these projects to the Hadza, please see ([Merrill et al., 2022][4]; [Olm et al., 2022][6]). ### Competing Interest Statement J.L.S. is a co-founder, shareholder, and on the scientific advisory board of Novome Biotechnologies and Interface Biosciences. [1]: #ref-1 [2]: #ref-23 [3]: #ref-20 [4]: #ref-40 [5]: #ref-53 [6]: #ref-46

Antimicrobial resistance has caused chaos worldwide due to the depiction of multidrug-resistant (MDR) infective microorganisms. A thorough examination of antimicrobial resistance (AMR) genes and associated resistant mechanisms is vital to solving this problem. Clostridium difficile (C. difficile) is …