28 - Fecal Microbiota Transplant Versus Antibiotics for Primary Clostridium Difficile Infection – a Multicenter, Randomized Proof-of-Concept Trial

Juul, Frederik Emil; Skudal, Hilde; Øines, Mari Nanna; Wiig, Håvard; Rose, Øystein; Seip, Birgitte; Furholm, Siv; Midtvedt, Tore; Kalager, Mette; Løberg, Magnus; Garborg, Kjetil; Bretthauer, Michael

doi:10.1016/s0016-5085(18)30517-1

Cited by 2 publications

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“…In human medical practice after the patients were treated with wide spectrum antibiotics the microbiome vanishes and they become susceptible to the aggressive and dangerous gut pathogen Clostridium difficile. The most effective treatment of this condition is the faecal transplantation from a healthy human donor (Juul et al, 2018). Other experiments indicate that upon infection of a resistant host animal, through the replacement of its microbiome with another, susceptible mouse's microbiome, these animals can be effectively infected by the pathogen too (Willing et al, 2011).…”

Section: Microbiome Succession Is Facilitated By Bacterial Conjugatio...mentioning

confidence: 99%

Domestication and microbiome succession may drive pathogen spillover

Apari

Földvári

2023

Front. Microbiol.

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Emerging infectious diseases have posed growing medical, social and economic threats to humanity. The biological background of pathogen spillover or host switch, however, still has to be clarified. Disease ecology finds pathogen spillovers frequently but struggles to explain at the molecular level. Contrarily, molecular biological traits of host-pathogen relationships with specific molecular binding mechanisms predict few spillovers. Here we aim to provide a synthetic explanation by arguing that domestication, horizontal gene transfer even between superkingdoms as well as gradual exchange of microbiome (microbiome succession) are essential in the whole scenario. We present a new perspective at the molecular level which can explain the observations of frequent pathogen spillover events at the ecological level. This proposed rationale is described in detail, along with supporting evidence from the peer-reviewed literature and suggestions for testing hypothesis validity. We also highlight the importance of systematic monitoring of virulence genes across taxonomical categories and in the whole biosphere as it helps prevent future epidemics and pandemics. We conclude that that the processes of domestication, horizontal gene transfer and microbial succession might be important mechanisms behind the many spillover events driven and accelerated by climate change, biodiversity loss and globalization.

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Section: Microbiome Succession Is Facilitated By Bacterial Conjugatio...mentioning

confidence: 99%

Domestication and microbiome succession may drive pathogen spillover

Apari

Földvári

2023

Front. Microbiol.

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“…In patients with long-term use of antibiotics or low immunity, the balance of intestinal flora is disrupted, such that C. difficile adheres to host intestinal epithelial cells, rapidly proliferates the intestinal niche, and produces toxins, such as C. difficile toxin A [TcdA] and C. difficile toxin B [TcdB] as well as binary toxins. These toxins trigger a cascade of cellular events that lead to fluid secretion, inflammation, and tissue damage, which bring about the symptoms of C. difficile infection (CDI), such as pseudomembranous colitis, toxic megacolon, and even death (Juul et al, 2018;Zhou et al, 2019;Rao and Malani, 2020).…”

Section: Introductionmentioning

confidence: 99%

Gut microbiome changes in mouse, Mongolian gerbil, and hamster models following Clostridioides difficile challenge

Wan,

You,

Shi

et al. 2024

Front. Microbiol.

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IntroductionClostridioides difficile infection (CDI), as well as its etiology and pathogenesis, have been extensively investigated. However, the absence of suitable CDI animal models that reflect CDI symptoms and the associated gut microbiome changes in humans has limited research progress in this field. Thus, we aimed to investigate whether Mongolian gerbils, which present a range of human pathological conditions, can been used in studies on CDI. Methods: In this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing.MethodsIn this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing.ResultsThe results obtained showed that C. difficile colonized the gastrointestinal tracts of the three rodents, and after the C. difficile challenge, C57BL/6J mice did not manifest CDI symptoms and their intestines showed no significant pathological changes. However, the hamsters showed explosive intestinal bleeding and inflammation and the Mongolian gerbils presented diarrhea as well as increased infiltration of inflammatory cells, mucus secretion, and epithelial cell shedding in their intestinal tissue. Further, intestinal microbiome analysis revealed significant differences with respect to intestinal flora abundance and diversity. Specifically, after C. difficile challenge, the Firmicutes/Bacteroidetes ratio decreased for C57BL/6J mice, but increased significantly for Mongolian gerbils and hamsters. Furthermore, the abundance of Proteobacteria increased in all three models, especially in hamsters, while that of Verrucomicrobia only increased significantly in C57BL/6J mice and Mongolian gerbils. Our results also indicated that differences in the relative abundances of Lactobacillaceae and Akkermansia were primarily responsible for the observed differences in response to C. difficile challenge.ConclusionBased on the observed responses to C. difficile challenge, we concluded for the first time that the Mongolian gerbil could be used as an animal model for CDI. Additionally, the taxa identified in this study may be used as biomarkers for further studies on CDI and to improve understanding regarding changes in gut microbiome in CDI-related diseases.

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28 - Fecal Microbiota Transplant Versus Antibiotics for Primary Clostridium Difficile Infection – a Multicenter, Randomized Proof-of-Concept Trial

Cited by 2 publications

References 0 publications

Domestication and microbiome succession may drive pathogen spillover

Domestication and microbiome succession may drive pathogen spillover

Gut microbiome changes in mouse, Mongolian gerbil, and hamster models following Clostridioides difficile challenge

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