Table 3.
Studies characterising changes in microbial diversity and profiles following FMT for UC
| Reference | Bioinformatic methodology | α + β Diversity (after FMT) |
Taxonomic Changes (after FMT) |
|||
|---|---|---|---|---|---|---|
| Responders | Non-responders | Responders | Non-responders | |||
| Paramsothy et al (2019)33 |
16S rRNA analysis MOTHUR pipeline Shotgun metagenomics Filtering - DeconSeq, FastQC Analysis - SolexaQA, MetaPhlAn2, HUMAnN2. |
In all patients α-diversity ↑ (Phylogenetic, richness and Shannon's diversity; P < 0.0001). β-diversity (multivariate dispersion) changed (P = 0.0001) following FMT, however these were more pronounced in patients entering remission |
↑ faecal + mucosal species richness ↑ Eubacterium hallii (Firmicutes), Roseburia inulinivorans (Firmicutes Lachnospiraceae), Eggerthella species and Ruminococcus bromii (Firmicutes Ruminococcus) ↑ Firmicutes (Oscillibacter and Clostridium XVIII) |
↓ faecal + mucosal species richness ↑ Fusobacterium (Fusobacterium gonidiaformans) (most consistent association), Sutterella (Sutterella wadsworthensis), Haemophilus, Escherichia, Megamonas, Clostridium XIVa, Prevotella (Prevotella copri) Dialister, Veillonella and Bilophila |
||
| Moayyedi et al (2015)8 |
16S rRNA analysis Analysis – Phyloseq R package and QIIME. |
α-diversity not reported Significant change in β-diversity (Bray-Curtis dissimilarity) following FMT with no association with clinical response. (P = 0.02) |
↑ Lachnospiraceae family and Ruminococcus in donor B (associated with successful FMT) | ↑ Escherichia and Streptococcus in donor A | ||
| Costello et al (2019)9 |
16S rRNA analysis Unspecified in-house and open source software. Differential abundance analysis lme4, mice, and glmmTMB R packages |
↑ α-diversity (OTU analysis) in all patients following FMT with no association with clinical response. β-diversity not reported |
↑ Methanobrevibacter smithii, Peptococcus niger (Firmicutes), Faecalicoccus pleomorphus (Firmicutes), Olsenella sp. (Actinobacteria), Acidaminococcus intestini (Firmicutes), Senegalimassilia anaerobia (Actinobacteria), Prevotella copri (Bacteroidetes), Clostridium methylpentosum (Firmicutes), Alistipes indistinctus (Bacteroidetes), Slackia isoflavoniconvertens (Actinobacteria) and Odoribacter splanchnicus strain (Bacteroidetes) ↓ Anaerostipes caccae, Gordonibacter pamelaeae and Clostridium aldenense Abundance change in Anaerofilum pentosovorans (Firmicutes), Bacteroides coprophilus (Bacteroidetes), Clostridium methylpentosum (Firmicutes), Acidaminococcus intestini (Firmicutes), Senegalimassilia anaerobia (Actinobacteria) |
Abundance change in Fusicatenibacter saccharivorans (Firmicutes) and Paraprevotella xylaniphila (Bacteroidetes) | ||
| Rossen et al (2015)10 |
16S rRNA analysis USEARCH algorithms and unspecified independent classification techniques. Differential abundance analysis using Canoco5 |
↑ α-diversity (Shannon's index, P = 0.06 (FMT-D), P = 0.01 (FMT-A)) β-diversity shift (redundancy) |
No change in diversity | ↑ Clostridium IV, XIVa and XVIII (Firmicutes)(FMT-D responders) ↓ Bacteroidetes (FMT-D responders) ↑ Bacilli, Proteobacteria and Bacteroidetes (FMT-A responders) |
None presented | |
| Crothers et al (2021)13 |
16s rRNA analysis QIIME2 pipeline |
No change in α-diversity (Shannon Index) | Taxonomic data not presented | |||
| Pai et al (2021)12 |
16S rRNA analysis Custom Perl scripts, Phyloseq R package and QIIME. |
α-diversity not reported β-diversity (unspecified measure) changed in FMT arm (not significant) – no association with clinical response |
Alistipes spp. and Escherichia spp. associated with achieving composite clinical outcome | None presented | ||
| Haifer et al (2021)11 |
16S rRNA analysis MOTHUR pipeline |
α diversity (richness) ↑ in all patients with changes seen in β-diversity (ANOSIM) following FMT. However, no change in α or β in relation to response or non-response. | Increase in Bacteroides OTU19 (100% similarity to Bacteroides ovatus and Bacteroides xylanisolvens) | Increase in Bacteroides OTU14 (100% similarity to Bacteroides caccae increase | ||
| Tian et al (2019)21 |
16S rRNA analysis Full pipeline not described. Differential analysis using LEfSe. |
α-diversity (Shannon index and Chao I index) and β-diversity (ANOVA) unchanged following FMT in all patients with no association with clinical response. | ↑ Bacteroidetes, Proteus, Prevotella, Phascolarctobacterium and Lactobacillus (d1), Clostridiaceae (d2) ↓ Firmicutes, Streptococcus |
↑ Bacteroidetes, Proteus ↓ Firmicutes, Streptococcus |
||
| Li et al (2020)22 |
16S rRNA analysis Combination of MOTHUR, UPARSE and R |
α-diversity ↑ (Shannon index and Chao I index) β-diversity (MDS) shift (trend) (both analogous to the donors). No separate data in responders |
↑ Holdemania Anaerostipes, Bifidobacterium, Clostridium IV and Odoribacter (analogous to donors) Eubacterium and Ruminococcus (close to donors) Differences in relative abundance of Eggerthella, Lactobacillus and Ruminococcus positively correlated to efficacy (P < 0.05) |
Notable difference in Eubacterium and Ruminococcus abundance compared with donors (P < 0.001) | ||
| Leonardi et al (2020)32 |
ITS1 analysis BLAST with ITS1 database fllowed by QIIME v1.6 Bacterial analysis as per Paramsothy et al. (2019)33 |
↑ bacterial α-diversity (↑ Candida pre-FMT had ↑ α-diversity 8 weeks post-FMT) No change to mycobiota diversity. No association with clinical response |
Reduction in abundance of Candida positively associated with clinical response |
No change in relative abundance of Candida | ||
| Kump et al (2018)23 |
16S rRNA analysis Combination of UCHIME, MOTHUR and QIIME v1.8 |
No change in α-diversity (richness) Significant change in β-diversity (unweighted UniFrac distance) |
↑ Akkermansia muciniphila ↓ Dialister |
No increase in A. muciniphila | ||
| Jacob et al (2017)24 |
16S rRNA analysis USEARCH and UPARSE algorithms / pipelines |
α-diversity ↑(OTUs P = 0.0049, Shannon index P = 0.069) Difference in β-diversity (Bray-Curtis dissimilarity) post-FMT (P < 0.034). No association with clinical response. |
No taxonomic data presented | |||
| Fang et al (2021)25 |
16S rRNA analysis Full pipeline not described. Differential analysis using LEfSe. |
No difference in α-diversity (Kruskal–Wallis rank sum). | ↑ Bacteroidetes and Prevotella and ↓ Proteobacteria and Escherichia post FMT. Association with clinical response data not presented. |
|||
| Cui et al (2015)26 |
16S rRNA analysis Not described. |
Microbial analysis only performed on a subset of patients (n=4). ↑ α-diversity seen in 3 patients post FMT (Pearson correlation coefficient) |
No taxonomic data presented | |||
| Chen et al (2020)27 |
16S rRNA analysis UPARSE and QIIME v1.7 |
↑ α-diversity (Shannon index) week 4 but then ↓ at week 12 – no association with clinical response | ↑ F. Prausnitzii (P < 0.05) – no association with clinical response | |||
| Brezina et al (2021)20 |
16S rRNA analysis QIIME2 pipeline. Differential analysis using LEfSe. |
α-diversity ↑ (Shannon entropy index) | ↑ Bacteroidales, Prevotellaceae, Veilllonellaceae and Desulfobacteria | ↑ Staphylococcaceae, Lactobacillaceae and Bifidobacteriaceae | ||
| Fuentes et al (2017)31 |
16S rRNA USEARCH algorithms and unspecified independent classification techniques. Differential abundance analysis using Canoco5 |
Analysis of TURN patients | ↑ Clostridium XIVa (Anaerostipes caccae, Coprococcus eutactus or Eubacterium rectale (similar levels to healthy donors)) ↓ Enterococcus, Proteobacteria Positive association to Clostridium IV (F. prausnitzii) and XIVa (Eubacterium hallii, Roseburia intestinalis and Butyrivibria crossotus) |
↓ Clostridium XIVa (Anaerostipes caccae, Coprococcus eutactus or Eubacterium rectale) ↑ Enterococcus, Proteobacteria and R. gnavus (P = 0.014) Positive association with Bacteroidetes groups (B. vulgatus and B. fragilis) |
||
| Goyal et al (2018)34 |
16S rRNA analysis QIIME pipeline. Differential analysis using LEfSe. |
↑ α-diversity (OTU) Change in β-diversity (weighted UniFrac) - both seen 1-month post-FMT. No statistically significant difference in α-diversity seen at 6 months post-FMT |
No significant increase in α-diversity (OTU) at 1- and 6-months post-FMT No change in β-diversity (weighted UniFrac) 1-month post-FMT |
↑ Lachnospiraceae and ↓ Enterobacteriaceae at 1 week, 1 month and 6 months post-FMT | ||
| Nishida et al (2016)36 |
16S rRNA analysis Full pipeline not described. Phyloseq R package for diversity analysis |
No difference in α- and β-diversity (Bray-Curtis dissimilarity index) at week 8 | No taxonomic data presented | |||
| Gogokhia et al (2020)39 |
Virome analysis Filtering using BBMAP following by analysis usin VirMAP pipeline |
Not reported | No change in relative abundance of Caudovirales bacteriophages 4 weeks post FMT | Increase in relative abundance of Caudovirales bacteriophages 4 weeks post FMT | ||
FMT-faecal microbiota transplantation, OUT-Operational taxonomic units, QIIME-Quantitative Insights Into Microbial Ecology, LEfSe-Linear discriminant analysis Effect Size, MDS-Multidimensional scaling