C Diff Molecular

Hiding in plain sight

Background The human microbiome plays an important role in modulating the host metabolism and immune system. Connections and interactions have been found between the microbiome of the gut and oral pharynx in the context of SARS-CoV-2 and other viral infections; hence, to broaden our understanding of host-viral responses in general and to deepen our knowledge of COVID-19, we performed a large-scale, systematic evaluation of the effect of SARS-CoV-2 infection on human microbiota in patients with varying disease severity. Results We processed 521 samples from 203 COVID-19 patients with varying disease severity and 94 samples from 31 healthy donors, consisting of 213 pharyngeal swabs, 250 sputa, and 152 fecal samples, and obtained meta-transcriptomes as well as SARS-CoV-2 sequences from each sample. Detailed assessment of these samples revealed altered microbial composition and function in the upper respiratory tract (URT) and gut of COVID-19 patients, and these changes are significantly associated with disease severity. Moreover, URT and gut microbiota show different patterns of alteration, where gut microbiome seems to be more variable and in direct correlation with viral load; and microbial community in the upper respiratory tract renders a high risk of antibiotic resistance. Longitudinally, the microbial composition remains relatively stable during the study period. Conclusions Our study has revealed different trends and the relative sensitivity of microbiome in different body sites to SARS-CoV-2 infection. Furthermore, while the use of antibiotics is often essential for the prevention and treatment of secondary infections, our results indicate a need to evaluate potential antibiotic resistance in the management of COVID-19 patients in the ongoing pandemic. Moreover, a longitudinal follow-up to monitor the restoration of the microbiome could enhance our understanding of the long-term effects of COVID-19. Video Abstract

Enteric pathogens increase C difficile virulence by providing amino acids that shape the metabolic environment in the gut.

Surveillance of Clostridioides difficile antimicrobial resistance in the United States

Objective Bariatric surgery is an effective treatment for type 2 diabetes (T2D) that changes gut microbial composition. We determined whether the gut microbiota in humans after restrictive or malabsorptive bariatric surgery was sufficient to lower blood glucose. Design Women with obesity and T2D had biliopancreatic diversion with duodenal switch (BPD-DS) or laparoscopic sleeve gastrectomy (LSG). Faecal samples from the same patient before and after each surgery were used to colonise rodents, and determinants of blood glucose control were assessed. Results Glucose tolerance was improved in germ-free mice orally colonised for 7 weeks with human microbiota after either BPD-DS or LSG, whereas food intake, fat mass, insulin resistance, secretion and clearance were unchanged. Mice colonised with microbiota post-BPD-DS had lower villus height/width and crypt depth in the distal jejunum and lower intestinal glucose absorption. Inhibition of sodium-glucose cotransporter (Sglt)1 abrogated microbiota-transmissible improvements in blood glucose control in mice. In specific pathogen-free (SPF) rats, intrajejunal colonisation for 4 weeks with microbiota post-BPD-DS was sufficient to improve blood glucose control, which was negated after intrajejunal Sglt-1 inhibition. Higher Parabacteroides and lower Blautia coincided with improvements in blood glucose control after colonisation with human bacteria post-BPD-DS and LSG. Conclusion Exposure of rodents to human gut microbiota after restrictive or malabsorptive bariatric surgery improves glycaemic control. The gut microbiota after bariatric surgery is a standalone factor that alters upper gut intestinal morphology and lowers Sglt1-mediated intestinal glucose absorption, which improves blood glucose control independently from changes in obesity, insulin or insulin resistance. Data are available on reasonable request.

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 common cancer in men worldwide. As infections have been associated with decreased cancer risk, the …

C. difficile strains with higher toxins levels induced an increased activation of the innate immune system and may activate macrophages more profoundly resulting in secretion of higher levels of pro-inflammatory cytokines. However, higher toxin levels may also damage macrophages' normal skele …

Thank you to the @AmCollegeGastro for this award! I’m excited to continue researching #Cdiff in #IBD. Big thank you to my mentors @UMichGIHep @UMichResearch Nobu Kamada @ibddoctor @a2binny Krishna Rao! Also thanks to @umfoodoc for a division that supports junior faculty! https://t.co/CaSNQCdG57— Kira Newman, MD, PhD (@KiraNewmanMDPhD) March 1, 2023

Cytomegalovirus (CMV) is a human herpes-type virus with variable clinical manifestations. Infections in immunocompetent patients are usually asymptomatic or mild, and severe infections are gener...

It's unknown whether clinical remission in patients with microscopic colitis is related to lavage-induced changes. New findings suggest that fecal microbial changes are not due to microscopic colitis itself but associated with stool form https://t.co/I8n7ObquZA— GutMicrobiota Health (@GMFHx) March 2, 2023

A recent animal study adds urgency to the fight against Clostridioides difficile infection, finding that the bacterium may be driving some colorectal cancers, which have risen among people younger than 50.

Clostridium perfringens type C and Clostridioides difficile are the main enteric clostridial pathogens of swine and are both responsible for neonatal diarrhea in this species. The role of Clostridum perfringes type A is under discussion. History, clinical signs, gross lesions and histological findin …

TCdA and TCdB affect directly the contractile reactivity of isolated rat colon smooth muscle. TCdA has a stronger direct effect on smooth muscle sensitivity to acetylcholine and 5-HT than TCdB. Such a trend has not been established for dopamine and norepinephrine.

Antibiotics can disrupt the flora of the gut or the gut microbiome. This can lead to gastrointestinal symptoms in some people, including constipation. Learn more here.

C. difficile is the primary cause for nosocomial infective diarrhoea. For a successful infection, C. difficile must navigate between resident gut bacteria and the harsh host environment. The perturbation of the intestinal microbiota by broad-spectrum antibiotics alters the composition …

Clostridioides difficile, a nosocomial pathogen, is an emerging gut pathobiont causing antibiotic-associated diarrhea. C. difficile infection involves gut colonization and disruption of the gut epithelial barrier, leading to the induction of inflammatory/immune responses. The expressio …

Some families of mobile elements in bacterial genomes encode not only a transposase but also an accessory TnpB gene. This gene has been shown to encode an RNA-guided DNA endonuclease, co-evolving with Y1 transposase and serine recombinase in mobile elements IS605 and IS607. In this pap …

Clostridioides difficile, a nosocomial pathogen, is an emerging gut pathobiont causing antibiotic-associated diarrhea. C. difficile infection involves gut colonization and disruption of the gut epithelial barrier, leading to the induction of inflammatory/immune responses. The expressio …

Study showed how Enterococcus fine tunes the environment around C. diff, restricting some nutrients and supplying others, to increase its fitness and virulence.

Understanding the interactions between C. difficile and the human gut offers new opportunities for heading off potentially fatal infections.

Risk factors for extraintestinal CDI include prior hospital stay, prolonged antibiotic therapy, proton pump inhibitor (PPI) use, relative state of immunodeficiency such as malnutrition and diabetes mellitus, previous abdominal surgery especially following perforation and leak of intestinal content.P …

Given the high prevalence of intestinal disease in humans and animals, there is a strong need for clinically relevant models recapitulating gastrointestinal systems, ideally replacing in vivo models in accordance with the principles of the 3R. We established a canine organoid system and analysed the …

Cytomegalovirus (CMV) is a human herpes-type virus with variable clinical manifestations. Infections in immunocompetent patients are usually asymptomatic or mild, and severe infections are gener...

Given the high prevalence of intestinal disease in humans and animals, there is a strong need for clinically relevant models recapitulating gastrointestinal systems, ideally replacing in vivo models in accordance with the principles of the 3R. We established a canine organoid system and analysed the …

Clostridioides difficile, a nosocomial pathogen, is an emerging gut pathobiont causing antibiotic-associated diarrhea. C. difficile infection involves gut colonization and disruption of the gut epithelial barrier, leading to the induction of inflammatory/immune responses. The expressio …

Diarrhea remains a common problem in clinical practice and attention must be paid to modifiable risk factors. Further research is needed on interventions to decrease its burden.

Risk factors for extraintestinal CDI include prior hospital stay, prolonged antibiotic therapy, proton pump inhibitor (PPI) use, relative state of immunodeficiency such as malnutrition and diabetes mellitus, previous abdominal surgery especially following perforation and leak of intestinal content.P …

Clostridioides difficile is the major cause of nosocomial diarrhea, which are associated with gut microbiome dysbiosis. Biofilms of C. difficile have been progressively linked to the pathogenesis of this bacterium and the recurrences of its infections. Though the number of conditions in which C. difficile biofilms are being produced is increasing, little is known about how and when biofilms are formed in the gut. Here we report that succinate, a metabolite abundantly produced by the dysbiotic gut microbiota, induces in vitro biofilm formation of C. difficile strains. We characterized the morphology and spatial composition of succinate-induced biofilms, and compared to non-induced or deoxycholate-induced biofilms, biofilms induced by succinate are significantly thicker, structurally more complex, and poorer in proteins and exopolysaccharides (EPS). We then applied transcriptomics and genetics to characterize the early stages of succinate-induced biofilm formation and we showed that succinate-induced biofilm results from major metabolic shifts and cell-wall composition changes. Similar to deoxycholate-induced biofilms, biofilms induced by succinate depend on the presence of a rapidly metabolized sugar. Finally, although succinate can be consumed by the bacteria, we found that the extracellular succinate is in fact responsible for the induction of biofilm formation through complex regulation involving global metabolic regulators and the osmotic stress response. In the context of human gut dysbiosis, succinate can limit bacterial infections through the control of innate immune responses. Collectively, our results suggest that succinate is an intestinal signal which can drive the biofilm formation and persistence of C. difficile in the gut and increase the risk of relapse. ### Competing Interest Statement The authors have declared no competing interest.