Bacterial profile to detect fungal taxa abundance in the gut
Inventors
Bajaj, Jasmohan • Gillevet, Patrick M.
Assignees
Virginia Commonwealth University • George Mason University
Publication Number
US-11253554-B2
Publication Date
2022-02-22
Expiration Date
2037-10-05
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Abstract
Disclosed herein are compositions and methods for diagnosing fungal dysbiosis in the gut of a subject with cirrhosis that involves assaying a sample from the subject for bacterial taxa. These compositions and methods are based on the discovery that there is significant correlation between fungal and bacterial diversity in gut microbiota of cirrhotic patients. Therefore, disclosed herein is a method for treating a subject with liver cirrhosis that involves assaying a gut sample from the subject for bacterial taxa to generate a bacterial profile, comparing the bacterial profile to control profiles to predict fungal dysbiosis; and treating the subject for fungal dysbiosis.
Core Innovation
The invention discloses compositions and methods for diagnosing fungal dysbiosis in the gut of subjects with cirrhosis by assaying a sample from the subject for bacterial taxa. This approach is based on the discovery of a significant correlation between fungal and bacterial diversity in the gut microbiota of cirrhotic patients. The method enables prediction of fungal taxa abundance, and thus fungal dysbiosis, solely through the analysis of bacterial profiles without the need to directly assay fungal components, which are harder to detect due to their low abundance and challenging DNA extraction.
The primary problem addressed is the difficulty in detecting fungal elements in gut samples from cirrhotic patients. Fungal cells are less abundant than bacteria and present challenges in efficient DNA extraction, making it experimentally difficult to detect the fungal component in fecal and oral samples. With increasing culture-negative and fungal infections in cirrhosis, a reliable, indirect method for assessing fungal dysbiosis is critical for patient management.
The disclosed method involves collecting a gut sample (such as stool, rectal swab, mucosal biopsy, or similar tissues/fluids), amplifying and sequencing bacterial DNA (notably the 16S rRNA gene), and generating a bacterial taxa profile. These bacterial profiles are then compared to control datasets to predict the state of fungal dysbiosis. In cases where fungal dysbiosis is predicted, the subject can be treated accordingly, for example with anti-fungal therapy, reducing antibiotics, or using probiotics, prebiotics, or fecal microbial transplant, depending on the inferred condition.
Claims Coverage
There is one independent claim which specifies the main inventive features of the invention.
Method for predicting and treating fungal dysbiosis in liver cirrhosis based on bacterial profiling
The inventive feature comprises the following steps: 1. Assaying a gastrointestinal bacterial sample from a subject with liver cirrhosis to generate a bacterial profile. 2. Comparing the bacterial profile to control profiles to predict fungal dysbiosis, wherein the prediction is based on a bacterial profile associated with fungal dysbiosis that comprises a reduction in bacterial diversity. 3. Treating the subject for fungal dysbiosis based on the prediction. This method relies exclusively on assessing bacterial taxa to inform on fungal status, without requiring direct detection of fungal components.
The main inventive feature is a method for predicting fungal dysbiosis in cirrhotic patients using only bacterial profiling, allowing for targeted treatment based on this indirect assessment.
Stated Advantages
The method can predict fungal taxa abundance in samples that are culture-negative for fungal infection.
It enables diagnosis of fungal dysbiosis based on easily accessible bacterial profiles, overcoming difficulties in direct fungal detection.
Allows for targeted treatment decisions such as antifungal therapy, reduction of antibiotic use, or microbiome repletion therapies based on predicted fungal status.
Provides a non-invasive and indirect approach for assessing gut fungal dysbiosis in cirrhotic patients.
Documented Applications
Diagnosing fungal dysbiosis in the gut of subjects with liver cirrhosis by analyzing bacterial profiles from gut samples.
Predicting which cirrhotic patients are likely to have fungal overgrowth and may benefit from anti-fungal therapy.
Identifying patients for whom excessive antibiotic use is indicated, allowing treatment by reduction or cessation of antibiotics.
Determining when microbiome depletion has occurred, guiding use of probiotics, prebiotics, or fecal microbial transplant for microbiome restoration.
Predicting risk of re-hospitalization within 90 days in patients with liver cirrhosis based on combined bacterial and fungal diversity metrics.
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