Bacteroides fragilis is a potential marker of effective microbiota transplantation in acute graft-versus-host disease treatment

Abstract

Summary Fecal microbiota transplantation (FMT), as any other medical procedure, requires standardization of results, approaches, monitoring of its dynamics and microbiota engraftment evaluation. The aim of the present study was to compare efficiency and results of PCR and 16S RNA-based sequencing in order to trace the dynamics of microbiota composition after FMT. Patients and methods The prospective, single-center study included 27 patients with acute intestinal and chronic (overlap syndrome) graft-versus-host disease (GvHD) developed after allogeneic hematopoietic stem cell transplantation (HSCT). FMT in 19 cases was performed, mostly, with ingestible capsules, eight placebo-treated patients were included into control group. Quantitative changes of different bacterial groups in fecal microbiota were assessed by means of real-time multiplex PCR, being compared with16S rRNA sequencing technique at the terms of D+3, D+16, D+30, D+60 and D+120 following FMT. Clinical response was determined by 4 scales evaluating intestinal syndrome and GvHD grade. Results When evaluating stool consistence according to Bristol scale as an index of GvHD therapy efficiency, we have observed complete clinical response by the D+120 after FMT in nine cases (47% with Bristol score of ≤4 points), and nine patients (47%) showed improved stool properties (>4 points). In the placebo group, complete or partial response was revealed, respectively, in one (13%), and four cases (50%) on the D+120. Multiplex PCR of fecal microbiota has shown a different time course in FMT- and placebo-treated patients, when compared to their initial (pre-FMT) levels. Total bacterial mass and copy numbers of distinct microbial species exhibited sufficient increase after FMT. Such shifts were demonstrable on D+30 for total microbial mass (p=0.002); Escherichia coli (p=0.001); Bacteroides fragilis group (p=0.05); Faecalibacterium prausnitzii (p=0.005). Meanwhile, the numbers Lactobacillus spp., and Bacteroides thetaiotaomicron, generally, were not changed over this time period. Moreover, in the control group (placebo) we have not found significant fecal microbiota changes against initial levels during 120 days monitoring period. Over 120 days of observation, we have also found some differences of the microbiota dynamics for the subgroups with complete response and partial/no response: Bifidobacterium spp. (р<0.047), E.coli (р<0.00047), B. fragilis group (p=5.6×10-5), F.prausnitzii (р<0.0062). Conclusions 1. Quantitative PCR of the major bacterial groups of gut microbiota, e.g., Bifidobacterium spp., E. coli, B. fragilis group, F. prausnitzii could be used as microbiological markers for evaluation of changing microbial landscape after FMT as a routine molecular biology technique. 2. The genocopy counts of B. fragilis group correlate with clinical response in the patients with intestinal GvHD after HSCT, either with, or without FMT procedure.

Systematic review with meta-analysis: encapsulated faecal microbiota transplantation – evidence for clinical efficacy

“…Goloshchapov and colleagues reported the successful treatment of steroid refractory acute or chronic GVHD with a complete response in five (38%) and partial response in 13 (100%) of the 13 treated patients 120 days after two to three days of FMT treatment. 65 In a case study, Mao and colleagues 67 reported the successful treatment of a 31-year-old male with steroid-refractory intestinal GVHD after two cycles of treatment with FMT.…”

“…In four studies, the safety and effects of encapsulated FMT on graft-versus-host disease in patients post allogeneic haemopoietic cell transplantation were examined in a total of 28 patients. [64][65][66][67] In a case study, Kaito and colleagues tested FMT as a third-line treatment in a patient with acute gut graft-versus-host disease (gGVHD) and concluded that improvement of diarrhoea from stage 3 (>1500 ml/day) to stage 1 (<500 ml/day) after two cycles of FMT was possibly caused by the treatment. 66 In an open-label pilot study by DeFilipp and colleagues 64 primarily investigating safety, FMT was considered safe and increased faecal diversity in the 13 treated patients.…”

“…Minor transient gastrointestinal adverse effects, such as diarrhoea, constipation, bloating and journals.sagepub.com/home/tag 13 flatulence, were described in the non-RCT studies (Supplementary Table 12). 61,63,65…”

Next-Generation Probiotics - The Future of Biotherapeutics

“…Bacteroides fragilis belongs to the Bacteroides species. The B. fragilis strains that lack the enterotoxin gene, display many major benefits (Round and Mazmanian, 2010;Goloshchapov et al, 2020). The capsular polysaccharide B. fragilis (PSA), which can modulate microbiota-host interactions, plays the most important function in this.…”

Human Exome Sequencing and Prospects for Predictive Medicine: Analysis of International Data and Own Experience

“…NGS applications in medical research are versatile. Via their intended use, high-throughput sequencing techniques can be split into the following groups: (1) analysis of entire genome (whole-genome sequencing, WGS); (2) analysis of protein-coding genes in a genome (whole-exome sequencing, WES); (3) analysis of particular disease-causing gene sequences (from clinical exomes embracing some 4000–5000 clinically relevant genes, to kits for small target regions of one–three genes or loci); (4) transcriptome sequencing (RNA-seq); and (5) analysis of bacterial microbiome biological diversity, Table 1 [ 1 , 7 ].…”