In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent <i>Clostridioides difficile</i> Infection
Importance: Although highly effective in treating recurrent <i>Clostridioides difficile</i> infection (RCDI), the mechanisms of action of fecal microbial transplantation (FMT) are not fully understood. Aim: The aim of this study was to explore microbially derived products or pathways tha...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | Microorganisms |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2607/11/4/1078 |
| _version_ | 1797604166079610880 |
|---|---|
| author | Monica Dahiya Juan Jovel Tanya Monaghan Karen Wong Wael Elhenawy Linda Chui Finlay McAlister Dina Kao |
| author_facet | Monica Dahiya Juan Jovel Tanya Monaghan Karen Wong Wael Elhenawy Linda Chui Finlay McAlister Dina Kao |
| author_sort | Monica Dahiya |
| collection | DOAJ |
| description | Importance: Although highly effective in treating recurrent <i>Clostridioides difficile</i> infection (RCDI), the mechanisms of action of fecal microbial transplantation (FMT) are not fully understood. Aim: The aim of this study was to explore microbially derived products or pathways that could contribute to the therapeutic efficacy of FMT. Methods: Stool shotgun metagenomic sequencing data from 18 FMT-treated RCDI patients at 4 points in time were used for the taxonomic and functional profiling of their gut microbiome. The abundance of the KEGG orthology (KO) groups was subjected to univariate linear mixed models to assess the significance of the observed differences between 0 (pre-FMT), 1, 4, and 12 weeks after FMT. Results: Of the 59,987 KO groups identified by shotgun metagenomic sequencing, 27 demonstrated a statistically significant change after FMT. These KO groups are involved in many cellular processes, including iron homeostasis, glycerol metabolism, and arginine regulation, all of which have been implicated to play important roles in bacterial growth and virulence in addition to modulating the intestinal microbial composition. Conclusion: Our findings suggest potential changes in key KO groups post-FMT, which may contribute to FMT efficacy beyond the restored microbial composition/diversity and metabolism of bile acids and short-chain fatty acids. Future larger studies that include a fecal metabolomics analysis combined with animal model validation work are required to further elucidate the molecular mechanisms. |
| first_indexed | 2024-03-11T04:42:31Z |
| format | Article |
| id | doaj.art-6332d293352d44a9b13a43f6974eb34c |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-11T04:42:31Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-6332d293352d44a9b13a43f6974eb34c2023-11-17T20:34:40ZengMDPI AGMicroorganisms2076-26072023-04-01114107810.3390/microorganisms11041078In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent <i>Clostridioides difficile</i> InfectionMonica Dahiya0Juan Jovel1Tanya Monaghan2Karen Wong3Wael Elhenawy4Linda Chui5Finlay McAlister6Dina Kao7Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, CanadaFaculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4Z6, CanadaNational Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UKFaculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, CanadaFaculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, CanadaFaculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, CanadaFaculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, CanadaFaculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, CanadaImportance: Although highly effective in treating recurrent <i>Clostridioides difficile</i> infection (RCDI), the mechanisms of action of fecal microbial transplantation (FMT) are not fully understood. Aim: The aim of this study was to explore microbially derived products or pathways that could contribute to the therapeutic efficacy of FMT. Methods: Stool shotgun metagenomic sequencing data from 18 FMT-treated RCDI patients at 4 points in time were used for the taxonomic and functional profiling of their gut microbiome. The abundance of the KEGG orthology (KO) groups was subjected to univariate linear mixed models to assess the significance of the observed differences between 0 (pre-FMT), 1, 4, and 12 weeks after FMT. Results: Of the 59,987 KO groups identified by shotgun metagenomic sequencing, 27 demonstrated a statistically significant change after FMT. These KO groups are involved in many cellular processes, including iron homeostasis, glycerol metabolism, and arginine regulation, all of which have been implicated to play important roles in bacterial growth and virulence in addition to modulating the intestinal microbial composition. Conclusion: Our findings suggest potential changes in key KO groups post-FMT, which may contribute to FMT efficacy beyond the restored microbial composition/diversity and metabolism of bile acids and short-chain fatty acids. Future larger studies that include a fecal metabolomics analysis combined with animal model validation work are required to further elucidate the molecular mechanisms.https://www.mdpi.com/2076-2607/11/4/1078fecal microbial transplantationrecurrent <i>Clostridioides difficile</i> infectionmetabolismintestinal dysbiosis |
| spellingShingle | Monica Dahiya Juan Jovel Tanya Monaghan Karen Wong Wael Elhenawy Linda Chui Finlay McAlister Dina Kao In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent <i>Clostridioides difficile</i> Infection Microorganisms fecal microbial transplantation recurrent <i>Clostridioides difficile</i> infection metabolism intestinal dysbiosis |
| title | In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent <i>Clostridioides difficile</i> Infection |
| title_full | In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent <i>Clostridioides difficile</i> Infection |
| title_fullStr | In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent <i>Clostridioides difficile</i> Infection |
| title_full_unstemmed | In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent <i>Clostridioides difficile</i> Infection |
| title_short | In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent <i>Clostridioides difficile</i> Infection |
| title_sort | in silico analysis of changes in predicted metabolic capabilities of intestinal microbiota after fecal microbial transplantation for treatment of recurrent i clostridioides difficile i infection |
| topic | fecal microbial transplantation recurrent <i>Clostridioides difficile</i> infection metabolism intestinal dysbiosis |
| url | https://www.mdpi.com/2076-2607/11/4/1078 |
| work_keys_str_mv | AT monicadahiya insilicoanalysisofchangesinpredictedmetaboliccapabilitiesofintestinalmicrobiotaafterfecalmicrobialtransplantationfortreatmentofrecurrenticlostridioidesdifficileiinfection AT juanjovel insilicoanalysisofchangesinpredictedmetaboliccapabilitiesofintestinalmicrobiotaafterfecalmicrobialtransplantationfortreatmentofrecurrenticlostridioidesdifficileiinfection AT tanyamonaghan insilicoanalysisofchangesinpredictedmetaboliccapabilitiesofintestinalmicrobiotaafterfecalmicrobialtransplantationfortreatmentofrecurrenticlostridioidesdifficileiinfection AT karenwong insilicoanalysisofchangesinpredictedmetaboliccapabilitiesofintestinalmicrobiotaafterfecalmicrobialtransplantationfortreatmentofrecurrenticlostridioidesdifficileiinfection AT waelelhenawy insilicoanalysisofchangesinpredictedmetaboliccapabilitiesofintestinalmicrobiotaafterfecalmicrobialtransplantationfortreatmentofrecurrenticlostridioidesdifficileiinfection AT lindachui insilicoanalysisofchangesinpredictedmetaboliccapabilitiesofintestinalmicrobiotaafterfecalmicrobialtransplantationfortreatmentofrecurrenticlostridioidesdifficileiinfection AT finlaymcalister insilicoanalysisofchangesinpredictedmetaboliccapabilitiesofintestinalmicrobiotaafterfecalmicrobialtransplantationfortreatmentofrecurrenticlostridioidesdifficileiinfection AT dinakao insilicoanalysisofchangesinpredictedmetaboliccapabilitiesofintestinalmicrobiotaafterfecalmicrobialtransplantationfortreatmentofrecurrenticlostridioidesdifficileiinfection |