C Diff Molecular

Understanding the principles of colonization resistance of the gut microbiome to the pathogen Clostridioides difficile will enable the design of defined bacterial therapeutics. We investigate the ecological principles of community resistance to C. difficile using a synthetic human gut microbiome. Us …

Clostridioides difficile infection in post-liver transplant patients was associated with higher mortality, readmission, healthcare cost, and longer length of stay. The most common cause of readmission was recurrent C. difficile infection which raises the question of the efficacy of standard first-li …

Clostridioides difficile flagellin FliC is associated with toxin gene expression, bacterial colonization, and virulence, and is also involved in pleiotropic gene regulation during in vivo infection. However, how fliC expression is regulated in C. difficile remains unclear …

The novel finding that formula exposure is correlated with a higher neonatal ARG burden lays the foundation that clinicians should consider feeding mode in addition to antibiotic use during the first months of life to minimize the proliferation of antibiotic-resistant gut bacteria in infants.Clinica …

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The objective of this study was to analyse the genetic relatedness of Clostridioides difficile polymerase chain reaction ribotype 017 (RT017) strains from patients with hospital-acquired C. difficile infection (HA-CDI) in a hospital with a high RT017 prevalence. From 2009 to 2013, 200 …

The Gram-positive, anaerobic bacterium Clostridioides difficile (CD) represents the most common cause of nosocomial diarrhea worldwide and is responsible for increased morbidity and mortality, and prolonged hospital stays [...].

Gastrointestinal illnesses are one of the most common comorbidities reported in patients with neurodevelopmental diseases, including autism spectrum disorders (ASD). Gut dysbiosis, overgrowth of C. difficile in the gut, and gut microbiota-associated alterations in central neurotransmission have been implicated in ASD, where the dopaminergic axis plays an important role in the disease pathogenesis. Human C. difficile strains produce a significant amount of the toxic metabolite p-cresol, an inhibitor of dopamine beta-hydroxylase (DBH), which catalyzes the conversion of dopamine (DA) to norepinephrine (NE). p-cresol is known to precipitate and exacerbate autistic behavior in rodents by increasing DA levels and altering DA receptor sensitivity in brain regions relevant to ASD. Therefore, we hypothesized that C. difficile infection dysregulates dopaminergic metabolism in the brain by increasing p-cresol levels in the gut and circulation and by inhibiting DBH, ultimately leading to elevated DA in the brain. For testing this hypothesis, we induced antibiotic-associated C. difficile in mice and determined the gut and serum p-cresol levels, serum DBH activity, and dopamine and its metabolite levels in different brain regions relevant to ASD. The results showed that C. difficile infection causes significant alterations in the dopaminergic axis in mice (p 0.05). In addition, significantly increased circulating p-cresol levels and reduced DBH activity was observed in C. difficile infected animals (p 0.05). Therefore, the results from this study suggest a potential link between C. difficile infection and alterations in the dopaminergic axis implicated in the precipitation and aggravation of ASD. ### Competing Interest Statement The authors have declared no competing interest.

Clostridioides difficile is an opportunistic diarrheal pathogen responsible for significant morbidity and mortality worldwide. A disrupted (dysbiotic) gut microbiome, commonly engendered by antibiotic treatment, is the primary risk factor for C. difficile infection, highlighting that C. difficile–microbiome interactions are critical for determining the fitness of this pathogen. Here, we review short chain fatty acids (SCFAs): a major class of metabolites present in the gut, their production by the gut microbiome, and their impacts on the biology of the host and of C. difficile. We use these observations to illustrate a conceptual model whereby C. difficile senses and responds to SCFAs as a marker of a healthy gut and tunes its virulence accordingly in order to maintain dysbiosis. Future work to learn the molecular mechanisms and genetic circuitry underlying the relationships between C. difficile and SCFAs will help to identify precision approaches, distinct from antibiotics and fecal transplant, for mitigating disease caused by C. difficile and will inform similar investigations into other gastrointestinal pathogens.

The gut microbiota has a key role in the maintenance of good health, and in the pathogenesis of gastrointestinal diseases. These conditions include the inflammatory bowel diseases, colorectal cancer, coeliac disease and metabolic liver disease. Although the nature of the microbial disturbance in the …

The importance of the detection of relevant toxins or toxin genes to diagnose Clostridioides difficile infection (CDI) or the prediction of clinical outcomes of CDI has been emphasized in recent years. Although stool culture of C. difficile is not routinely recommended in the era of nonculture metho …

Author summary Secondary bile acid production by the colonic microbiome strongly correlates with an environment that is resistant to C. difficile invasion. However, it remained unclear if these bile acids provided in vivo protection. Here, we show that members of the microbiome that generate secondary bile acids (e.g., C. scindens) protect against C. difficile disease independently of secondary bile acid generation. These results are important because efforts to restore colonization resistance (e.g., FMT or precision bacterial therapy) focus on restoring secondary bile acid generation. Instead, restoring the organisms that produce 5-aminovalerate or consume proline / glycine are more important.

@MVazquezRoqueMD is known as “The Queen of Poop” come join us now to find out why. Join here: https://t.co/jc48rg0SNQ… @Khanna_S @DarrellPardi Dr. Robert Orenstein @MDMagazine #CDiff— Melissa Kaplan (@MelissaKaplan01) October 14, 2021

C. difficile — the leading cause of hospital-associated intestinal infections — induces a rapid influx of bile acids into the gut, which could provide a novel target for blocking infection.

Prognostic factors for sCDI and rCDI could aid clinicians to make treatment decisions based on risk stratification. We suggest that future studies use standardized definitions for sCDI/rCDI and systematically collect and report the risk factors assessed in this review, to allow for meaningful meta-a …

Girinathan et al. define complex mechanisms by which individual gut commensals limit or worsen Clostridioides difficile pathogenicity. Integrated, high-resolution analyses of metabolomic, metatranscriptomic and phenotypic outcomes identify complex intermicrobe interactions in vivo to delineate how commensals uniquely shape the intestinal environment to impact microbial programs, which may enlighten bacteriotherapeutic approaches.

Microbe types in older people’s intestines are different and are linked to disease

We present predictive models for comprehensive systems analysis of Clostridioides difficile, the etiology of pseudomembranous colitis. By leveraging 151 published transcriptomes, we generated an EGRIN model that organizes 90% of C. difficile genes into a transcriptional regulatory network of 297 co- …

Leveraging systems biology approaches, we illustrate how metabolically distinct species of Clostridia protect against or worsen Clostridioides difficile infection in mice by modulating the pathogen's colonization, growth, and virulence to impact host survival. Gnotobiotic mice colonized with the ami …

CDI remains an urgent public health threat and continues to be the most frequent cause of diarrhea among hospitalized patients and overall hospital-acquired infection in the United States.

Tetracyclines and macrolides, two commonly used classes of antibiotics, stop beneficial gut bacteria from growing and ultimately kill them, a study published Wednesday by Nature found.

For the first time, investigators proved that a higher presence of Clostridioides difficile bacteria and toxins cause a more severe infection.

Leveraging systems biology approaches, we illustrate how metabolically distinct species of Clostridia protect against or worsen Clostridioides diffici…

The gut controls the health of the entire body -- give your patients a once-over gut check challenge to start eating healthy and...

Estimated to cause almost half a million infections per year, the bacterium Clostridioides difficile, also known as C. difficile or "C. diff," can cause diarrhea and inflammation of the large intestine. ...

As identified in this analysis, patients with risk factors for rCDI could be candidates for close monitoring, a high index of suspicion, and risk mitigation interventions to avoid rCDI and improve clinical outcomes.

For iCDI, the performance largely hinges on the incidence, which even for hospitalized patients can be low (often