Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

Hudson, Lauren E.; Anderson, Sarah E.; Corbett, Anita H.; Lamb, Tracey J.

doi:10.1128/cmr.00049-16

Cited by 61 publications

(44 citation statements)

References 380 publications

(438 reference statements)

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“…An important role for Veillonella in CDI is supported by the fact that Veillonella species were associated with low coprostanol levels that correlated strongly with CDI 53 . A similar negative relationship between Moryella species and CDI has previously been observed 57 . Enterococcus, a feature selected from the classification of CDI vs. Non-CDI Diarrhea, has been reported to be associated with CDI due to vancomycin resistance 58 .…”

Section: Discussionsupporting

confidence: 86%

A Computational Framework to Quantify Host-Microbiome Interactions in Clostridioides Difficile Infection

Ke¹,

Pollock²,

Xu-wen³

et al. 2020

Preprint

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Background: Clostridioides difficile infection (CDI) is the most common cause of healthcare–associated infection and an important cause of morbidity and mortality among hospitalized patients. A comprehensive understanding of C. difficile infection (CDI) pathogenesis is crucial for disease diagnosis, treatment and prevention. To achieve that, a quantitative study of host-microbiome interactions in CDI is a prerequisite. Yet, an effective computational framework to quantify host-microbiome interactions in CDI was lacking. Methods: Here, we characterized gut microbial compositions and abroad panel of immunological markers in a comprehensive clinical cohort of 243 well-characterized human subjects with four different C. difficile infection/colonization statuses (CDI, Asymptomatic Carriage, Non-CDI Diarrhea, and Control). Based on microbial and immunological features, we developed a computational framework to detect CDI status using random forest and symbolic classification models.Results: First, by calculating the correlations between microbial compositions and the circulating levels of host immune markers for each of the four phenotype groups, we found that the interactions between gut microbiota and host immune markers are very sensitive to the status of C. difficile colonization and infection. Second, we demonstrated that incorporating both gut microbiome and host immune marker data into random forest classifiers can better distinguish CDI from other groups than can either type of data alone. Finally, we performed symbolic classification using selected features from random forest classifiers to derive simple mathematic formulas that explicitly model the interactions between gut microbiome and host immune markers.Conclusions: Overall, this study provides an effective computational framework to quantify the role of the intricate interactions between gut microbiota and host immune markers in CDI pathogenesis. This framework may inform the design of future diagnostic and therapeutic strategies.

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Section: Discussionsupporting

confidence: 86%

A Computational Framework to Quantify Host-Microbiome Interactions in Clostridioides Difficile Infection

Ke¹,

Pollock²,

Xu-wen³

et al. 2020

Preprint

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“…Results also highlight the need for in-depth evaluation of the clinical significance of these gut changes and potentially associated intestinal and generalized inflammation during long-duration spaceflight. The evidence from our fecal transplantation experiments provides strong support for the development of probiotic-based countermeasures to improve the intestinal homeostasis in astronauts (75). In addition to its potential significance in spaceflight research, the results may also shed light on the improvement of intestinal homeostasis in patients with functional gastrointestinal disorders.…”

Section: Discussionmentioning

confidence: 55%

Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model

Shi

Wang

et al. 2017

FASEB j.

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Exposure to microgravity leads to alterations in multiple systems, but microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground-based controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes. The colon epithelium of HU mice showed decreased goblet cell numbers, reduced epithelial cell turnover, and decreased expression of genes that are involved in defense and inflammatory responses. As a result, increased susceptibility to dextran sulfate sodium-induced epithelial injury was observed in HU mice. Cohousing of Ctrl mice with HU mice resulted in HUlike epithelial changes in Ctrl mice. Transplantation of feces from Ctrl to HU mice alleviated these epithelial changes in HU mice. Results indicate that HU changes intestinal microbiota, which leads to altered colonic epithelial cell homeostasis, impaired barrier function, and increased susceptibility to colitis. We further demonstrate that alteration in gastrointestinal motility may contribute to HU-associated dysbiosis. These animal results emphasize the necessity of evaluating astronauts' intestinal homeostasis during distant space travel.-Shi, J., Wang, Y., He, J., Li, P., Jin, R., Wang, K., Xu, X., Hao, J., Zhang, Y., Liu, H., Chen, X., Wu, H., Ge, Q. Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model. FASEB J. 31, 3695-3709 (2017 Exposure to microgravity leads to alterations, such as bone demineralization, muscle atrophy, cardiovascular deconditioning, and immune dysfunction, in multiple systems (1). Limited reports also suggest that spaceflight and microgravity affect the integrity of intestinal epithelium. For instance, reduced length of villi and depth of crypts was found in rats that were flown on 12-d Cosmos 2044 and Foton M3 missions (2, 3), and decreased mucin production of intestinal epithelial cells was shown in rats that were flown on the 19.5-d Cosmos 605 mission (4). Colonic TGF-b expression was altered in mice aboard the 13-d STS-135 or 91-d International Space Station missions (5, 6). Using a well-accepted, ground-based spaceflight analog, the hindlimb unloading (HU) mouse model (7) found that simulated microgravity resulted in a transient increase in intestinal permeability, which is characterized by the elevation of circulating LPS and the activation of the innate immune system. The clinical significance and mechanism of these epithelial changes are not clear; however, Chopra et al. (8) reported that HU mice that were infected with Salmonella enterica serovar typhimurium had a 100-fold decrease in LD 50 compared with normal-gravity control (Ctrl) mice. This indicates that microgravity-induced intestinal epithelial changes may exacerbate bacte...

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“…Such a development would enhance our therapeutic arsenal to fight intestinal infections, such as these are caused by C. difficile. Moreover, it has been estimated that the change in the diet and the use of prebiotics or probiotics could possibly restore the colonization resistance against C. difficile [119,120]. Reducing antimicrobial use would arguably reduce antimicrobial-resistant organisms.…”

Section: Restoration Of the Gut Microbiota As Therapeutic For CDImentioning

confidence: 99%

Insights into the Role of Human Gut Microbiota in Clostridioides difficile Infection

Kachrimanidou

Tsintarakis

2020

Microorganisms

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Clostridioides difficile infection (CDI) has emerged as a major health problem worldwide. A major risk factor for disease development is prior antibiotic use, which disrupts the normal gut microbiota by altering its composition and the gut’s metabolic functions, leading to the loss of colonization resistance and subsequent CDI. Data from human studies have shown that the presence of C. difficile, either as a colonizer or as a pathogen, is associated with a decreased level of gut microbiota diversity. The investigation of the gut’s microbial communities, in both healthy subjects and patients with CDI, elucidate the role of microbiota and improve the current biotherapeutics for patients with CDI. Fecal microbiota transplantation has a major role in managing CDI, aiming at re-establishing colonization resistance in the host gastrointestinal tract by replenishing the gut microbiota. New techniques, such as post-genomics, proteomics and metabolomics analyses, can possibly determine in the future the way in which C. difficile eradicates colonization resistance, paving the way for the development of new, more successful treatments and prevention. The aim of the present review is to present recent data concerning the human gut microbiota with a focus on its important role in health and disease.

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Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

Cited by 61 publications

References 380 publications

A Computational Framework to Quantify Host-Microbiome Interactions in Clostridioides Difficile Infection

A Computational Framework to Quantify Host-Microbiome Interactions in Clostridioides Difficile Infection

Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model

Insights into the Role of Human Gut Microbiota in Clostridioides difficile Infection

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Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

Cited by 61 publications

References 380 publications

A Computational Framework to Quantify Host-Microbiome Interactions in Clostridioides Difficile&nbsp;Infection

A Computational Framework to Quantify Host-Microbiome Interactions in Clostridioides Difficile&nbsp;Infection

Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model

Insights into the Role of Human Gut Microbiota in Clostridioides difficile Infection

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A Computational Framework to Quantify Host-Microbiome Interactions in Clostridioides Difficile Infection

A Computational Framework to Quantify Host-Microbiome Interactions in Clostridioides Difficile Infection