BIOM&S Seminar

SPEAKERS;   Cailin Harris and Jessmyn Niergarth (Bioinformatics students)

Calin's TITLE :  Understanding the Changes in Microbiome Composition of Clostridiodes Difficile Patients Pre and Post Fecal Microbiota Transplantation

ABSTRACT:   In recent years, the use of fecal microbiota transplantation (FMT) has been found to be an effective way to treat patients with refractory or recurrent Clostridiodes difficile infection (rCDI). Despite the increase in using it as a treatment option, the exact mechanism that makes FMT a successful treatment is still unknown and finding key microbes that play important roles in the success of FMT has become a primary objective for FMT research and this study Here, we describe the changes in the microbiome of 58 patients with rCDI treated with FMT over 4 different timepoints: baseline (pre-FMT), Day 10, Week 5, and Week 13 post-FMT. Healthy samples from 7 donors that made up 193 dose samples were used as a control group for comparison. MOTHUR was used to preprocess the short-read sequencing data and generate taxonomic classification of bacterial DNA. Bacterial diversity was found to greatly increase post-FMT with the most noticeable increase at the Day 10 timepoint. Our findings indicate that bacteria from the phyla Firmicutes and Actinobacteria may be augmented after FMT. Specifically, the families Lachnospiraceae and Clostridiales from Firmicutes were noted to increase in abundance post-FMT. The phyla Verrucomicrobia and Bacteroidetes are shown to be engrafted into the patient microbiome from the donor microbiome and Proteobacteria is shown to deplete after treatment indicating an association with the infected gut. These results suggest that these might be key bacteria in restoring the gut microbiome of rCDI patients. In congress with health or clinical information, metabolomic, and virome data, we hope to develop donor matching and personalized bacterial treatments for patients. Information regarding engrafted and augmented bacteria in patients with rCDI following FMT treatment can lead to a wealth of understanding regarding the mechanisms of successful FMT. Obtaining a list of the microbes for the restoration of rCDI to a healthy gut microbiota community can help to develop a safe and synthetic cocktail of targeted bacteria therapy for rCDI or CDI.

Jessmyn's TITLE:   Gut bacteriophage dynamics, fecal microbiota transplantation, and recurrent or refractory Clostridioides difficile infection

ABSTRACT:  Clostridioides difficile infection (CDI) is an issue in healthcare settings around the world. CDI can recur after or be refractory to antibiotic treatment, in which cases it is called rCDI. rCDI may be cured with fecal microbiota transplantation (FMT), a treatment whose mechanism of action and long-term risks are not completely understood. FMT success could be affected by bacteriophages (phages), which are viruses that infect bacteria and could influence human gut microbiota functions. This analysis considered the phages of 25 rCDI patients who were cured of rCDI using FMT in a recent clinical trial. Fecal samples were collected from patients pre-FMT and at three time points post-FMT (10 days, 5 weeks, and 13 weeks after last FMT). Virus-like particles from the samples were purified and their DNA was amplified, then sequenced using Illumina MiSeq. No well-established pipeline for phage metagenomics exists, so one was constructed to filter, mask, assemble, and identify the reads. Concurrently with fecal sample collection, patients answered the RAND 36-Item Health Survey to assess health-related quality of life. Associations between “Bodily Pain”, a measure from the survey, and relative abundances of phages were analyzed. To discover phages of interest, all phages identified were filtered based on overall abundance, then based on association with Bodily Pain in individual mixed models. Joint analysis of the associations between remaining phages and Bodily Pain were then performed using a lasso-type variable selection method. 36 phages were identified as targets for further study.