A human gut ecosystem protects against C. difficile disease by targeting TcdA

Martz, Sarah; Guzman-Rodriguez, Mabel; He, Shan; Noordhof, Curtis; Hurlbut, David; Gloor, Gregory B.; Carlucci, Christian; Weese, Scott; Allen‐Vercoe, Emma; Sun, Jun; Claud, Erika C.; Petrof, Elaine O.

doi:10.1007/s00535-016-1232-y

Cited by 24 publications

(23 citation statements)

References 66 publications

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“…Many studies have also demonstrated that Lactobacillus and Bifidobacterium are associated with colonization resistance against C. difficile (Lawley et al, 2012;Petrof et al, 2013;Valdes-Varela et al, 2016;Martz et al, 2017;De Wolfe et al, 2018;Vedantam et al, 2018). Bifidobacterium longum JDM301, a widely used commercial probiotic strain, can inhibit C. difficile growth and degrade TcdA and TcdB, and the author further proved that the exertion of inhibition of B. longum is dependent on an acidic pH (Wei et al, 2018).…”

Section: Introductionmentioning

confidence: 94%

Consortium of Probiotics Attenuates Colonization of Clostridioides difficile

Chu

Huang

et al. 2019

Front. Microbiol.

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Clostridioides difficile infection (CDI) is increasing morbidity and mortality rates globally. Fecal microbiota transplantation (FMT), an effective therapy for eliminating Clostridioides difficile (C. difficile), cannot be used extensive due to a range of challenges. Probiotics thus constitutes a promising alternative therapy. In our study, we evaluated the effect of consortium of probiotics including five Lactobacilli strains and two Bifidobacterium strains on the colonization of toxigenic BI/NAP1/027 C. difficile in a mouse model. The results of 16S rRNA sequencing and targeted metabolomics showed the consortium of probiotics effectively decreased the colonization of C. difficile, changed the αand β-diversity of the gut microbiota, decreased the primary bile acids, and increased the secondary bile acids. Spearman's correlation showed that some of the OTUs such as Akkermansia, Bacteroides, Blautia et al. were positively correlated with C. difficile numbers and the primary bile acids, and negatively correlated with the secondary bile acids. However, some of the OTUs, such as Butyricicoccus, Ruminococcus, and Rikenellaceae, were negatively correlated with C. difficile copies and the primary bile acids, and positively correlated with the secondary bile acids. In summary, the consortium of probiotics effectively decreases the colonization of C. difficile, probably via alteration of gut microbiota and bile acids. Our probiotics mixture thus offers a promising FMT alternative.

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Section: Introductionmentioning

confidence: 94%

Consortium of Probiotics Attenuates Colonization of Clostridioides difficile

Chu

Huang

et al. 2019

Front. Microbiol.

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“…With respect to well-established defined communities, the probiotic cocktail VSL#3 and the fecal transplant substitute MET-1 have been tested on various human or animal intestinal cell lines (Caco-2, T84, and HT-29) (e.g., see references [138][139][140]. In most studies, however, the use of bacterial lysates or conditioned media was preferred over live bacteria (e.g., see references 72 and 141-144), because the (mainly anaerobic) gut bacteria cannot survive under the aerobic conditions needed for intestinal cell culture.…”

Section: Modeling the Host In Vitromentioning

confidence: 99%

The Use of Defined Microbial Communities To Model Host-Microbe Interactions in the Human Gut

Elzinga

Oost

Vos

et al. 2019

Microbiol Mol Biol Rev

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SUMMARYThe human intestinal ecosystem is characterized by a complex interplay between different microorganisms and the host. The high variation within the human population further complicates the quest toward an adequate understanding of this complex system that is so relevant to human health and well-being. To study host-microbe interactions, defined synthetic bacterial communities have been introduced in gnotobiotic animals or in sophisticatedin vitrocell models. This review reinforces that our limited understanding has often hampered the appropriate design of defined communities that represent the human gut microbiota. On top of this, some communities have been applied toin vivomodels that differ appreciably from the human host. In this review, the advantages and disadvantages of using defined microbial communities are outlined, and suggestions for future improvement of host-microbe interaction models are provided. With respect to the host, technological advances, such as the development of a gut-on-a-chip system and intestinal organoids, may contribute to more-accuratein vitromodels of the human host. With respect to the microbiota, due to the increasing availability of representative cultured isolates and their genomic sequences, our understanding and controllability of the human gut “core microbiota” are likely to increase. Taken together, these advancements could further unravel the molecular mechanisms underlying the human gut microbiota superorganism. Such a gain of insight would provide a solid basis for the improvement of pre-, pro-, and synbiotics as well as the development of new therapeutic microbes.

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“…Many pharmaceutical firms are actively working to bring easily consumable CDI-targeted drugs based on FMT. A defined microbial ecosystem therapeutics (MET-1 or RePOOPulate) was developed to cure recurrent CDI [136,137]. The closest enema-based drug that is awaiting clinical approval is RBX2660, which depends upon the microbial suspension provided from the donor and is formulated for therapeutic delivery.…”

Section: In Treating Diseases Associated With Gut Microbiota-associatmentioning

confidence: 99%

The Therapeutic Potential of the “Yin-Yang” Garden in Our Gut

Srikumar¹,

Fanning²

2019

Role of Microbes in Human Health and Diseases

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The gut microbiota is made up of trillion microorganisms comprising bacteria, archaea, and eukaryota living in an intimate relationship with the host. This is a highly diverse microbial community and is essentially an open ecosystem despite being deeply embedded in the human body. The gut microbiome is continually exposed to allochthonous bacteria that primarily originates from food intake. Comprising more than 1000 bacterial species, the gut microbiota endows so many different functions-so many that can be considered as an endocrine organ of its own. In this book chapter, we summarize the importance of gut microbiota in the development and maintenance of a healthy human body. We first describe how the gut microbiota is formed during the birth of a human baby and how a healthy microflora is established overtime. We also discuss how important it is to maintain the microbiota in its homeostatic condition. A discussion is also given on how alterations in the microbiota are characteristic of many diseased conditions. Recent investigations report that reestablishing a healthy microbiota in a diseased individual using fecal microbial transplant can be used as a therapeutic approach in curing many diseases. We conclude this chapter with a detailed discussion on fecal microbial transplants.

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A human gut ecosystem protects against C. difficile disease by targeting TcdA

Cited by 24 publications

References 66 publications

Consortium of Probiotics Attenuates Colonization of Clostridioides difficile

Consortium of Probiotics Attenuates Colonization of Clostridioides difficile

The Use of Defined Microbial Communities To Model Host-Microbe Interactions in the Human Gut

The Therapeutic Potential of the “Yin-Yang” Garden in Our Gut

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