SER-109, an Oral Microbiome Therapy for Recurrent
            <i>Clostridioides difficile</i>
            Infection

Feuerstadt, Paul; Louie, Thomas; Lashner, Bret A.; Wang, Elaine E. L.; Diao, Liyang; Bryant, Jessica A.; Sims, Matthew; Kraft, Colleen S.; Cohen, Stuart H.; Berenson, Charles S.; Korman, Louis Y.; Ford, Christopher B.; Litcofsky, Kevin; Lombardo, Mary‐Jane; Wortman, Jennifer; Wu, Henry; Auniņš, John G.; McChalicher, Christopher W.J.; Winkler, Julian; McGovern, Barbara; Trucksis, Michele; Henn, Matthew R.; Moltke, Lisa von

doi:10.1056/nejmoa2106516

Cited by 229 publications

(180 citation statements)

References 37 publications

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“…difficile recurrence in all age groups studied (recurrence, SER-109 vs. placebo, 12% vs. 40%; relative risk, 0.32; 95% confidence interval, 0.18–0.58, P < 0.001). The safety profile was similar to placebo ( 125 ). FMT and microbial replacement products require more study to understand the mechanisms, microbes, and durability by which these therapeutics alter gut microbiome function and drive clinical outcomes ( 126 ).…”

Section: Development Of Therapeutics From Ngs and The Microbiomementioning

confidence: 75%

Next-generation sequencing: insights to advance clinical investigations of the microbiome

Wensel¹,

Pluznick²,

Salzberg³

et al. 2022

Journal of Clinical Investigation

130

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Next-generation sequencing (NGS) technology has advanced our understanding of the human microbiome by allowing for the discovery and characterization of unculturable microbes with prediction of their function. Key NGS methods include 16S rRNA gene sequencing, shotgun metagenomic sequencing, and RNA sequencing. The choice of which NGS methodology to pursue for a given purpose is often unclear for clinicians and researchers. In this Review, we describe the fundamentals of NGS, with a focus on 16S rRNA and shotgun metagenomic sequencing. We also discuss pros and cons of each methodology as well as important concepts in data variability, study design, and clinical metadata collection. We further present examples of how NGS studies of the human microbiome have advanced our understanding of human disease pathophysiology across diverse clinical contexts, including the development of diagnostics and therapeutics. Finally, we share insights as to how NGS might further be integrated into and advance microbiome research and clinical care in the coming years.

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Section: Development Of Therapeutics From Ngs and The Microbiomementioning

confidence: 75%

Next-generation sequencing: insights to advance clinical investigations of the microbiome

Wensel¹,

Pluznick²,

Salzberg³

et al. 2022

Journal of Clinical Investigation

130

View full text Add to dashboard Cite

show abstract

“…The most direct example of host protection conferred by the gut microbiota is through colonization resistance against mucosal pathogens like Clostridium difficile. Extensive mechanistic and clinical evidence has demonstrated that disruption of the intestinal microbiota by antibiotics plays a causal role in C. difficile infection of the gut, whereas restoration of a diverse intestinal microbiota through fecal transplant or microbial consortia therapy can be curative [4][5][6] . A diverse gut microbiota aides the host in resisting pathogen colonization through various mechanisms including inter-microbial competition for nutrients, metabolic competition, and direct antagonism/killing strategies 7 , as well as fortification of mucosal barrier integrity 8,9 and local mucosal immune defenses 10 .…”

Section: The Intestinal Microbiota and Host Defense Against Infectionsmentioning

confidence: 99%

Long-distance relationships - regulation of systemic host defense against infections by the gut microbiota

et al. 2022

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“…Based on these findings, cFMT represents a less cumbersome, more practical, and more flexible approach for patients to restore gut microbiota diversity with the advantage that it can be administered in the outpatient setting. More standardized, oral products, such as SER-109, composed of purified Firmicutes spores ( McGovern et al., 2021 ), are also showing promising results in preventing recurrence of C. difficile infection ( Feuerstadt et al., 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Encapsulated Fecal Microbiota Transplantation: Development, Efficacy, and Clinical Application

Halaweish

Staley

2022

Front. Cell. Infect. Microbiol.

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Fecal microbiota transplantation (FMT) has been established as a highly restorative therapeutic approach for treating recurrent Clostridioides difficile infection (rCDI). Recently, the use of capsule-based fecal microbiota transplantation (cFMT) has been shown to be a clinically effective approach to restore intestinal microbiota composition. This convenient, oral delivery provides an easy route of administration and a newfound flexibility for clinicians and patients. In this review, we discuss the development of cFMT, paying particular attention to lyophilized cFMT products. We review the available published clinical studies comparing cFMT with lower endoscopic FMT (eFMT) or placebo. We further discuss the pharmacokinetics of FMT, which should be understood in a framework of microbial ecology that considers the complex and dynamic interactions of gut microbiota with host factors and other microorganisms. Promisingly, the results of multiple trials investigating cFMT vs. eFMT in rCDI show cFMT to be as effective as eFMT at preventing rCDI. However, its efficacy in non-rCDI conditions, including obesity and metabolic syndrome, inflammatory bowel disease, HIV, and neurologic conditions, is less clear and more research is needed in these areas. Standardization of formulation, dose, and timing of administration to ensure optimal microbiota engraftment and clinical response is also a challenge to be addressed. Overall, cFMT is a practical method for fecal microbiota transplantation, with similar efficacy to eFMT in the resolution of rCDI, that holds therapeutic potential in a variety of other diseases.

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SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection

Cited by 229 publications

References 37 publications

Next-generation sequencing: insights to advance clinical investigations of the microbiome

Next-generation sequencing: insights to advance clinical investigations of the microbiome

Long-distance relationships - regulation of systemic host defense against infections by the gut microbiota

Encapsulated Fecal Microbiota Transplantation: Development, Efficacy, and Clinical Application

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