Sound the (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide pGpp - PubMed
It has recently become evident that the bacterial stringent response is regulated by a triphosphate alarmone (pGpp) as well as the canonical tetra- and pentaphosphate alarmones ppGpp and pppGpp [together, (p)ppGpp]. Often dismissed in the past as an artifact or degradation product, pGpp has been con …
Bile salt hydrolases shape the bile acid landscape and restrict Clostridioides difficile growth in the murine gut - PubMed
Bile acids (BAs) mediate the crosstalk between human and microbial cells and influence diseases including Clostridioides difficile infection (CDI). While bile salt hydrolases (BSHs) shape the BA pool by deconjugating conjugated BAs, the basis for their substrate selectivity and impact on C. difficil …
Host sorbitol and bacterial sorbitol utilization promote C. difficile infection in inflammatory bowel disease - PubMed
Sorbitol and sorbitol utilization in the infecting C. difficile strain play major roles for the pathogenesis and epidemiology of CDI in IBD patients. CDI in IBD patients may thus be avoided or improved by elimination of dietary sorbitol or suppression of host-derived sorbitol production.
Clostridioides difficile Binary Toxin Binding Component Increases Virulence in a Hamster Model - PubMed
Overall, this study demonstrates that the binding component of C difficile binary toxin, CDTb, contributes to virulence in a hamster model of infection.
The findings identify methods to better prevent and treat C.difficle, the most common cause of antibiotic-associated diarrhea and healthcare-acquired infections (HAIs).
Researchers find new strategies to treat Clostridioides difficile infections
Researchers at Brigham and Women's Hospital (BWH) and Massachusetts General Hospital (MGH), two of the founding institutions of Mass General Brigham, have discovered the metabolic mechanisms Clostridioides difficile uses to quickly invade the gut.
Assessment of microbiota in the gut and upper respiratory tract associated with SARS-CoV-2 infection - Microbiome
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
Human gut microbiota after bariatric surgery alters intestinal morphology and glucose absorption in mice independently of obesity
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.
Clostridium difficile Infection Is Associated With Decreased Prostate Cancer Risk: A Retrospective Cohort Study - PubMed
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 …
The effect of different C. difficile MLST strains on viability and activity of macrophages - PubMed
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 Colitis in a Patient With Ulcerative Colitis on Vedolizumab Monotherapy
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
Study Suggests C Diff Infections May Drive Colorectal Cancer
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.
Clostridial diarrheas in piglets: A review - PubMed
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 …
Clostridium difficile toxins impact on rat colon smooth muscle reactivity - PubMed
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.
Relevancia y necesidades del síndrome del intestino irritable (SII): comparación con la enfermedad inflamatoria intestinal (EII). (Por favor, si no te interesa el SII, léelo.) | Gastroenterología y Hepatología
Can antibiotics cause constipation: What is the link?
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.
Clostridioides difficile infection: traversing host-pathogen interactions in the gut - PubMed
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 …
Host Immune Responses to Surface S-Layer Proteins (SLPs) of Clostridioides difficile - PubMed
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 …
Phylogenetic Relationships among TnpB-Containing Mobile Elements in Six Bacterial Species - PubMed
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 …
Host Immune Responses to Surface S-Layer Proteins (SLPs) of Clostridioides difficile - PubMed
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 …