Identification and engraftment of new bacterial strains by shotgun metagenomic sequence analysis in patients with recurrent Clostridioides difficile infection before and after fecal microbiota transplantation and in healthy human subjects

• Published in: PloS one Vol. 16; no. 7; p. e0251590
• Main Authors: Verma, Sandeep, Dutta, Sudhir K., Firnberg, Elad, Phillips, Laila, Vinayek, Rakesh, Nair, Padmanabhan P.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.07.2021; Public Library of Science (PLoS)
• Subjects: Abundance; Adult; Aged; Antibiotics; Authorship; Bacteria; Bacteria - classification; Bacteria - genetics; Bacteria - isolation & purification; Bacterial infections; Biology and Life Sciences; Campylobacter; Care and treatment; Causes of; Clostridioides difficile - genetics; Clostridioides difficile - isolation & purification; Clostridium difficile; Clostridium Infections - microbiology; Clostridium Infections - therapy; Colitis; Deoxyribonucleic acid; DNA; DNA sequencing; Donors; Dysbacteriosis; Dysbiosis - microbiology; Dysbiosis - therapy; E coli; Ecology and Environmental Sciences; Endoscopy; Fatty acids; Fecal Microbiota Transplantation; Fecal microflora; Feces; Feces - microbiology; Female; Gastroenterology; Gastrointestinal Microbiome; Gastrointestinal system; Gastrointestinal tract; Health aspects; Health care; Hepatitis; HIV; Hospitals; Human immunodeficiency virus; Humans; Identification and classification; Infections; Klebsiella; Laboratories; Male; Mathematical analysis; Medicine and Health Sciences; Metagenome; Metagenomics; Metagenomics - methods; Methods; Microbiomes; Microbiota; Middle Aged; Nucleotide sequencing; Pathogens; Patient outcomes; Patients; Public health; Recurrence; Recurrent infection; Relative abundance; Salmonella; Sequence analysis; Strains (organisms); Transplantation; Transplants & implants; United States; United States > US; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0251590

Recurrent Clostridioides diffícile infection (RCDI) is associated with major bacterial dysbiosis and colitis. Fecal microbiota transplantation (FMT) is a highly effective therapeutic modality for RCDI. While several studies have identified bacterial species associated with resolution of symptoms in patients, characterization of the fecal microbiome at the bacterial strain level in RCDI patients before and after FMT and healthy donors, has been lacking. The aim of this study was to examine the ability of bacterial strains from healthy donors to engraft in the gastrointestinal tract of patients with RCDI following FMT. Fecal samples were collected from 22 patients with RCDI before and after FMT and their corresponding healthy donors. Total DNA was extracted from each sample and analyzed by shotgun metagenomic sequencing. The Cosmos-ID analysis platform was used for taxonomic assignment of sequences and calculation of the relative abundance (RA) of bacterial species and strains. From these data, the total number of bacterial strains (BSI), Shannon diversity index, dysbiosis index (DI), and bacterial engraftment factor, were calculated for each strain. A marked reduction (p<0·0001) in the RA of total and specific bacterial strains, especially from phylum Firmicutes, was observed in RCDI patients prior to FMT. This change was associated with an increase in the DI (p<0·0001) and in pathobiont bacterial strains from phylum Proteobacteria, such as Escherichia coli O157:H7 and Klebsiella pneumoniae UCI 34. BSI was significantly lower in this group of patients as compared to healthy donors and correlated with the Shannon Index. (p<0·0001). Identification and engraftment of bacterial strains from healthy donors revealed a greater diversity and higher relative abundance of short-chain fatty acid (SCFA)-producing bacterial strains, including Lachnospiraceae bacterium 5_1_63FAA_u_t, Dorea formicigenerans ATCC 27755, Anaerostipes hadrusand others, in RCDI patients after FMT. These observations identify a group of SCFA-producing bacterial strains from healthy donors that engraft well in patients with RCDI following FMT and are associated with complete resolution of clinical symptoms and bacterial dysbiosis.