Fecal fungome and therapeutic efficacy of fecal microbiota transplantation

a technology of fecal microorganisms and fungi, which is applied in the direction of microorganisms, plant/algae/fungi/lichens ingredients, and drug compositions, etc., can solve the problems of ineffective fmt, poor outcome, and negative impact on the therapeutic effect of fmt, so as to suppress the growth or proliferation of c and improve the effect of efficacy

Inactive Publication Date: 2021-02-11
THE CHINESE UNIVERSITY OF HONG KONG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0011]Related compositions useful in FMT with improved efficacy may comprise (1) a donor stool material containing live fecal microorganisms and (2) an antifungal agent that specifically suppresses the growth or proliferation of C. albicans but exhibits no such suppressive or inhibitory effect against other fungal species. Instead of a broad-spectrum fungicide, such specific anti-C. albicans agent may be short polynucleotide in nature of (e.g., a small inhibitory RNA, microRNA, miniRNA, lncRNA, or an antisense oligonucleotide that is capable of disrupting the expression of a key gene in the life cycle of C. albicans) that is capable of specifically targeting the species only but not other closely related fungal species.

Problems solved by technology

In particular, the present inventor discovered that, when elevated level of the yeast species Candida albicans is present in the gastrointestinal tract of an FMT recipient or in the stool of an FMT donor, therapeutic efficacy of FMT is negatively impacted.
An elevated C. albicans level before or after FMT is indicative of a higher likelihood of poor outcome or ineffective FMT.

Method used

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  • Fecal fungome and therapeutic efficacy of fecal microbiota transplantation
  • Fecal fungome and therapeutic efficacy of fecal microbiota transplantation
  • Fecal fungome and therapeutic efficacy of fecal microbiota transplantation

Examples

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example 1

Introduction

[0056]Fecal microbiota transplantation (FMT) is effective in treating recurrent Clostridium difficile infection (CDI) and is increasingly being utilized in other human diseases. Whilst bacteria colonization in recipients after FMT has been established, little is known of the role of the gut mycobiota. In this study the present inventors show gut fungal dysbiosis in CDI and identify that donor-derived fungi colonization in recipient is associated with FMT response. Mycobiota profiling in CDI reveals over-presentation of C. albicans and decreased fungal diversity, richness and evenness compared with healthy controls. Cure after FMT was observed when donor-derived fungal taxa predominated in recipients' mycobiota. FMT responders display a high prevalence of Saccharomyces and Aspergillus whilst non-responders and individuals treated with antibiotics display a dominant presence of Candida. High abundance of C. albicans in recipient before FMT and in donor stool nullifies FMT ...

example 2

C. albicans Level Associated with Unfavorable FMT Outcome in IBD

[0107]The fecal C. albicans level was investigated in three IBD patients with concurrent CDI, and subsequently followed them up after FMT (FIG. 21). Disease symptoms were ameliorated soon after FMT. However, all three patients manifested unfavorable FMT outcomes at different time-points post FMT. In accordance with the finding for CDI patients, these IBD patients all showed increased fecal C. albicans levels after FMT. Taken into consideration the previous observation that C. albicans levels were also higher in IBD than in Controls (FIG. 18), it indicates that C. albicans may play an unfavorable role in IBD and IBD-FMT.

[0108]All patents, patent applications, and other publications, including GenBank Accession Numbers, cited in this application are incorporated by reference in the entirety for all purposes.

TABLE 1Duration ofOutcomeSevere / follow up(till lastSubjectSexAgeSmokingModerate(wks)follow up)FMT1M80Ex-smokerModera...

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Abstract

Methods are provided for identifying subjects as suitable donor or recipients for FMT, for assessing the likelihood of FMT treatment success, and for enhancing FMT treatment efficacy. Also provided are kits and compositions for FMT with enhanced efficacy.

Description

BACKGROUND OF THE INVENTION[0001]This application claims priority to U.S. Provisional Patent Application No. 62 / 625,705, filed Feb. 2, 2018, and U.S. Provisional Patent Application No. 62 / 679,417, filed Jun. 1, 2018, the contents of both are hereby incorporated by reference in the entirety for all purposes.BACKGROUND OF THE INVENTION[0002]Clostridium difficile infection (CDI) is a symptomatic infection due to the spore-forming bacterium, Clostridium difficile. C. difficile infection is spread by bacterial spores found within feces. Risk factors for infection include antibiotic or proton pump inhibitors use, hospitalization, other health problems, and older age. Its symptoms including watery diarrhea, fever, nausea, and abdominal pain, CDI makes up about 20% of cases of antibiotic-associated diarrhea. About 453,000 cases C. difficile infection occurred in the United States in 2011, resulting in 29,000 deaths. Each year, C. difficile infections accounts for health care cost of approxi...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K36/064A61P1/12C12N1/20
CPCA61K36/064C12R1/725C12N1/20A61P1/12C12Q1/689C12Q2600/106C12Q1/6883C12N1/165C12R2001/725
Inventor NG, SIEW CHIENZUO, TAOCHAN, KA LEUNG FRANCIS
Owner THE CHINESE UNIVERSITY OF HONG KONG
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