The effect of a microbial ecosystem therapeutic (MET-2) on recurrent Clostridioides difficile infection: a phase 1, open-label, single-group trial

Kao, Dina; Wong, Karen; Ratzinger, Franz; Cochrane, Kyla; Sherriff, Keith; Chui, Linda; Lloyd, Colin; Roach, Brandi; Bai, Anthony D.; Petrof, Elaine O.; Allen‐Vercoe, Emma

doi:10.1016/s2468-1253(21)00007-8

Cited by 51 publications

(32 citation statements)

References 35 publications

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“… 58 Therefore, future studies on infant gut microbiome remediation could focus on the use of defined microbial mixtures for both enhanced safety and targeted efficacy, as has been done for the treatment of recurrent Clostridioides difficile infection in adults. 80 Further, it is recommended that clinical variables should be considered sequentially for infant microbiome studies, first by dispersal limitation factors (e.g., delivery mode, environment such as hospital versus home or urban versus rural, probiotics) then by habitat filtering factors (e.g., diet, prebiotics, antibiotics).…”

Section: Discussionmentioning

confidence: 99%

Bacteroidota and Lachnospiraceae integration into the gut microbiome at key time points in early life are linked to infant neurodevelopment

et al. 2021

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Section: Discussionmentioning

confidence: 99%

Bacteroidota and Lachnospiraceae integration into the gut microbiome at key time points in early life are linked to infant neurodevelopment

et al. 2021

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“…They also showed that a small subset of the Abs strongly reacted with the S-protein of SARS-CoV, whereas a second distinct subset of Abs reacted moderately with a combination of the MET-1 and MET-2 communities of commensal microbiota (Fig. 3C) (33,34). None of the Abs reacted with negative control BSA (Fig.…”

Section: Isolation Of Mabs From S-proteinreactive Pre-existing Tonsillar B Cellsmentioning

confidence: 96%

SARS-CoV-2–Reactive Mucosal B Cells in the Upper Respiratory Tract of Uninfected Individuals

Liu

Budylowski

Dong

et al. 2021

The Journal of Immunology

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SARS-CoV-2 is a respiratory pathogen that can cause severe disease in at-risk populations but results in asymptomatic infections or a mild course of disease in the majority of cases. We report the identification of SARS-CoV-2–reactive B cells in human tonsillar tissue obtained from children who were negative for coronavirus disease 2019 prior to the pandemic and the generation of mAbs recognizing the SARS-CoV-2 Spike protein from these B cells. These Abs showed reduced binding to Spike proteins of SARS-CoV-2 variants and did not recognize Spike proteins of endemic coronaviruses, but subsets reacted with commensal microbiota and exhibited SARS-CoV-2–neutralizing potential. Our study demonstrates pre-existing SARS-CoV-2–reactive Abs in various B cell populations in the upper respiratory tract lymphoid tissue that may lead to the rapid engagement of the pathogen and contribute to prevent manifestations of symptomatic or severe disease.

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“…The demonstration that either a defined consortium of commensal bacteria or spores derived from healthy donor stool deliver efficacy comparable with that of conventional FMT in treating rCDI support the concept that the bacterial component of FMT is a key contributor to efficacy. 53 – 55 Of further particular interest has been the demonstration that sterile filtered FMT also is efficacious for treating rCDI. 56 Collectively, these data suggest that soluble factors related to bacteria – but not necessarily intact bacteria per se – are important mediators of the efficacy of FMT, with potential explanations including bacterial products (e.g., enzymes or other proteins), associated bacteriophages, or gut microbial metabolites.…”

Section: Impact Of CDI Treatments Upon Gut Microbiome–bile Acid Interactionsmentioning

confidence: 99%

The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection

Mullish

Allegretti

2021

Therap Adv Gastroenterol

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Clostridioides difficile infection (CDI) remains a major global cause of gastrointestinal infection, with significant associated morbidity, mortality and impact upon healthcare system resources. Recent antibiotic use is a key risk factor for the condition, with the marked antibiotic-mediated perturbations in gut microbiome diversity and composition that underpin the pathogenesis of CDI being well-recognised. However, only relatively recently has further insight been gained into the specific mechanistic links between these gut microbiome changes and CDI, with alteration of gut microbial metabolites – in particular, bile acid metabolism – being a particular area of focus. A variety of in vitro, ex vivo, animal model and human studies have now demonstrated that loss of gut microbiome members with bile-metabolising capacity (including bile salt hydrolases, and 7-α-dehydroxylase) – with a resulting alteration of the gut bile acid milieu – contributes significantly to the disease process in CDI. More specifically, this microbiome disruption results in the enrichment of primary conjugated bile acids (including taurocholic acid, which promotes the germination of C. difficile spores) and loss of secondary bile acids (which inhibit the growth of C. difficile, and may bind to and limit activity of toxins produced by C. difficile). These bile acid changes are also associated with reduced activity of the farnesoid X receptor pathway, which may exacerbate C. difficile colitis throughout its impact upon gut barrier function and host immune/inflammatory response. Furthermore, a key mechanism of efficacy of faecal microbiota transplant (FMT) in treating recurrent CDI has been shown to be restoration of gut microbiome bile metabolising functionality; ensuring the presence of this functionality among defined microbial communities (and other ‘next generation’ FMT products) designed to treat CDI may be critical to their success.

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The effect of a microbial ecosystem therapeutic (MET-2) on recurrent Clostridioides difficile infection: a phase 1, open-label, single-group trial

Cited by 51 publications

References 35 publications

Bacteroidota and Lachnospiraceae integration into the gut microbiome at key time points in early life are linked to infant neurodevelopment

Bacteroidota and Lachnospiraceae integration into the gut microbiome at key time points in early life are linked to infant neurodevelopment

SARS-CoV-2–Reactive Mucosal B Cells in the Upper Respiratory Tract of Uninfected Individuals

The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection

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