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. 2023 Sep 18;11(9):2562. doi: 10.3390/biomedicines11092562

Table 2.

Studies investigating the effect of cIMDs on the intestinal microbiota.

First Author/
Year/Ref.		 Species Tested cIMDs Changes Observed (Yes/No) Observed Effects
Bajaj et al., 2018 [41] Humans, LT Peri-operative:
GC + MMF.
Manteinance: TAC + MMF
CyA + MMF 		YES

  1. Increase in α-diversity after LT

  2. Decreased abundance after LT of Enterobacteriaceae (Escherichia, Shigella, Salmonella)

  3. Increased abundance after LT of Ruminococcaceae and Lachnospiraceae
Bhat et al., 2017 [42] Rats, normal TAC or SIR YES

  1. No difference in α-diversity

  2. No difference in the Firmicutes/Bacteroidetes ratio

  3. Higher abundance in the SIR and TAC groups of Akkermansia muciniphila, Roseburia, Oscillospira, Mollicutes, Rothia, Micrococcaceae, Actinomycetales and Staphylococcus
Bitto et al., 2016 [43] Mice, normal aging SIR YES Higher abundance of segmented filamentous bacteria (Candidatus Arthromitus sp.) in the SIR group
de Lima et al., 2022 [44] Rats, PTZ-kindling PREDN YES

  1. No change in α-diversity

  2. No difference in the abundance of Firmicutes or Bacteirodetes

  3. Higher abundance in the PREDN 1 mg/kg group (but not in the 5 mg/kg group) of Verrucomicrobia, Saccharibacteria and Actinobacteria

  4. Higher abundance, at the family level, of Porphyromonadaceae, Verrucomicrobiaceae and Clostridiaceae_1 in the PREDN 1 mg/kg and 5 mg/kg groups, and of Erysipelotrichaceae only in the PREDN 1 mg/kg group and of Eubacteriaceae in the PREDN 5 mg/group

  5. Higher abundance, at the genus level, of Lactobacillus, Barnesiella, and Akkermansia in PREDN 5 mg/kg and 1 mg/kg groups and of Ruminococcus only in the 1 mg/kg group

  6. Higher abundance, at the species level, of Muribaculum intestinale and Akkermansia muciniphila in the PREDN 5 mg/kg and 1 mg/kg groups and of Saccharibacteria_genera_incertae_sedis TM7_phylum only in the 5 mg/kg group
Flannigan et al., 2018 [45] Mice, normal MMF YES

  1. Lower α-diversity in the MMF group

  2. Lower abundance in the MMF group at the phylum level of Bacteroidetes and Verrucomicrobia and at genus level of Akkermansia, Parabacteroides and Clostridium

  3. Higher abundance in the MMF group, at the phylum level, of Proteobacteria and at the genus level of Escherichia/Shigella
Han et al., 2019 [46] Mice, normal TAC
TAC ± ABX		 YES

  1. Increase in α-diversity in the TAC group partially reverted by ABX

  2. Decrease in α-diversity with TAC + ABX

  3. Lower abundance of Verrucomicrobia in the TAC group

  4. Higher abundance in the TAC + ABX group of Verrucomicrobia, family Verrucomicrobiaceae, genus Akkermansia

  5. Lower abundance in the TAC + ABX group of Firmicutes, family Lachnospiraceae, genus Coprococcus

  6. Lower Firmicutes/Bacteroidetes ratio in the TAC + ABX group
Han et al., 2021 [47] Mice, normal SIR YES

  1. Lower abundance in the SIR group at the phylum level of Cyanobacteria, Firmicutes, and Verrucomicrobia, at the family level of Verrucomicrobiaceae and, at the genus level, of Akkermansia

  2. Higher abundance in the SIR group at the phylum level of Proteobacteria, at the family level of Helicobacteriaceae, Desufovibrionaceae and Alcaligenaceae, and, at the genus level, of Sutterella, Desulfovibrio and Helicobacter

He et al., 2019 [48] Mice, SLE (MRL/lpr mice) PRED YES

  1. No difference in α-diversity.

  2. Lower abundance in the PRED group at the phylum level of Proteobacteria and Deferribacteres, and, at genus level, of Rikenella, Mucispirillum, Oscillospira and Bilophila

  3. Higher abundance in the PRED group at the genus level of Prevotella and Anaerostipes

Hurez et al., 2015 [49] Mice, normal SIR YES

  1. Minor differences in the composition of fecal microbiota

  2. Higher abundance in the SIR group of four taxa: Lactobacillus Intestinalis spp., and unclassified Acidobacteriaceae and Rikenellaceae (two taxa)
Jia et al., 2019 [50] Rats, LT CyA YES

  1. Higher α-diversity in the CyA group

  2. Higher abundance in the CyA group, in comparison with controls, of Enterococcus spp.

  3. Lower abundance in the CyA group, in comparison with controls, of Faecalibacterium prausnitzii, Clostridium cluster XI, and Clostridium cluster XIV

  4. Lower abundance in the CyA group, in comparison with the allograft group, of Faecalibacterium prausnitzii, Enterobacteriaceae spp., Clostridium cluster I and Clostridium cluster XIV
Jiang et al., 2018 [51] Rat, LT TAC YES

  1. Higher α-diversity in the TAC group

  2. Higher abundance of Bacteroides-Prevotella, Enterococcus faecalis and Enterobacteriaceae in the TAC group

  3. Lower abundance Faecalibacterium prausnitzii and Bifidobacterium spp. in the TAC group
Jiao et al. 2019 [52] Mice, normal TAC YES

  1. No difference in α-diversity

  2. Higher abundance in the TAC group of Alistipes, Allobaculum, and Bacteroides

  3. Lower abundance in the TAC group of NK4A136, UCG-014, and Akkermansia
Jung et al., 2016 [53] Mice, DIO SIR YES

  1. No difference in the Firmicutes/Bacteroidetes ratio

  2. Lower abundance in the non-obese SIR group as compared with non-obese control mice, at the genus level, of Alloprevotella, Ruminococcus, Bifidobacterium, Marvinbryantia, Helicobacter, and Coprobacillus

  3. Lower abundance in the obese SIR group as compared with non-obese control mice, at the genus level, of Turicibacter, unclassified Marinilabiliaceae, Alloprevotella, unclassified Porphyromonadaceae, Ruminococcus, Bifidobacterium, Marvinbryantia, Helicobacter, and Coprobacillus
Kamata et al., 2020 [54] Humans, AIP PREDN YES

  1. No PREDN-induced change in α-diversity

  2. PREDN-induced disappearance of Enterobacteriales (at the order level) and of Klebsiellae at the genus level

  3. PREDN-induced increase in the abundance of Ruminococcus
Kang et al., 2019 [55] Humans, children with NS PRED YES

  1. No change in α-diversity induced by PRED

  2. PRED-induced increase in the abundance of Deinococcus Thermus and Acidobacteria (at the phylum level), and at the genus level of Romboutsia, Stomatobaculum, Cloacibacillus, Howardella, Mobilitalea, Deinococcus, Paracoccus, Stenotrophomonas, Gp1, Kocuria, Pseudomonas, Acinetobacter, Brevundimonas and Lactobacillus bacteria

  3. PRED-induced decrease in the abundance of Finegoldia and Corynebacterium
Lähteenmäki et al., 2017 [56] Humans, children with HSCT CyA+ (MTX and MMF only in 1 patient) YES

  1. Higher abundance in HSCT, at phylum level, of Proteobacteria, and, at the genus level, of Enterococcus, Staphylococcus, Enterobacter, Bacteroides and unclassified genera of Lachnospriracea

  2. Lower abundance in HSCT, at phylum level, of Firmicutes, Actinobacteria and Bacterodeites and, at the genus level, of Bifidobacterium, Bacteroides, Blautia and Faecalibacterium (especially F. prausnitzii)
Llorenç et al., 2022 [57] Mice, EAU MMF YES

  1. Higher α-diversity in the MMF group

  2. Higher Firmicutes/Bacteroidetes ratio in the MMF group

  3. Higher abundance, at the genus level, of Muribaculum, Bifidobacterium, Anaerostipes and Firmicutes UGC-005 in the MMF group compared with control mice

  4. Lower abundance, at the genus level, of Bacteroides, Monoglobus, Eisenbergiella and Lachnospiraceae UCG-001 in the MMF group compared with control mice

  5. Higher abundance of Lachnospiraceae NK4A136 in the EAU-MMF group compared with control EAU mice

  6. Lower abundance of Lachnospiraceae UCG-001 in the EAU-MMF group compared with control EAU mice
Lyons et al., 2018 [58] Mice, experimental colitis SIR NO No change in fecal microbiota induced by SIR
Pigneur et al., 2019 [59] Humans, children with CD PRED YES

  1. PRED-induced a marginal increase in a-diversity

  2. PRED increased the abundance at genus level, of Ruminococcus and Bifidobacterium, and at species level, of bacterium M62, A186, Faecalibacterium prausnitzii Roseburia intestinalis, Eubacterium and Bifidobacterium bifidum

  3. PRED-decreased, at the genus level, the abundance of Blautia
Qiu et al., 2019 [60] Humans, TM PRED YES

  1. PRED decreased α-diversity

  2. At the phylum level, GC increased Actinobacteria and the Firmicutes/Bacteroidetes ratio

  3. At the genus level, GC decreased Bacteroides, Bifidobacterium, Eubacterium and increased Streptococcus and Geobacillus
Robles-Vera et al., 2020 [61] Rat, DOCA salt hypertension MMF YES

  1. Decrease in α-diversity (vs. DOCA-rats)

  2. Lower abundance in the MMF group, at the phylum level, of Firmicutes and, at genus level, of Lactobacillus and Sutterella

  3. Higher abundance in the MMF group, at the phylum level, of Bacteroidetes

Robles-Vera et al., 2021 [62] Rats, SHR MMF YES

  1. No effect on α-diversity

  2. The Firmicutes/Bacteroidetes ratio was higher in SHR than in control rats and it was normalized by MMF

  3. Higher abundance in the MMF group in comparison with SHR of the Sutterella genus

  4. Lower abundance in the MMF group in comparison with SHR of the Clostridium genus

  5. Higher abundance, at the phylum level, of Firmicutes and, at genus level, of Lactobacillus in the SHR group, normalized by MMF

  6. Higher abundance, at the phylum level, of Actinobacteria and Bacteroidetes in the SHR group, normalized by MMF
Schepper et al., 2020 [63] Mice, GC-induced osteoporosis PREDN YES

  1. Lower abundance of Verrucomicobiales and Bacteriodales in the PREDN group

  2. Higher abundance of Clostridiales in the PREDN group
Simpson et al., 2022 [33] Humans, KT TAC + MMF YES

  1. No difference in α-diversity between KTR and controls.

  2. Higher abundance in KTR, at class level, of Gammaproteobacteria, Bacilli and Erysipelotrichia

  3. Lower abundance in KTR, at class level, Actinobacteria and Verrucomicrobiae
Sivaraj et al., 2022 [64] Humans, LT TAC + SIR + PRED YES

  1. Higher Firmicutes/Bacteroidetes ratio in LTR

  2. Higher abundance in LTR at phylum level of Firmicutes and Proteobacteria and, at family level, of Enterobacteriaceae, Erysipelotrichaceae, Fusobacteriaceae, Lactobacillaceae, and Veillonellaceae at 3 months post-LT and of Lachnospiraceae, Ruminococcaceae, Streptococcaceae, and Staphylococcaceae after 6 months

  3. In comparison to pre-transplant samples, Firmicutes (in particular Clostridiaceae) were increased 3 months after LT and Lachnospiraceae and Ruminococcaceae 6 months post-LT
Swarte et al., 2020 [65] Human, KT CyA (18%)
TAC (57%)
AZT (9%)
MMF (72%)
PRED (96%)		 YES

  1. Lower α-diversity in KTR than in age-matched controls. Changes in α-diversity positively correlated with MMF use

  2. Higher abundance in KTR, at the phylum level, of Proteobacteria, and, at species level of Escherichia coli sp.

  3. Lower abundance in KTR, at the phylum level, of Actinobacteria and, at species level of Bifidobacterium sp., Streptococcus termophylus, Blautia wexlerae and Streptococcus mitis

  4. No difference in firmicutes
Taylor et al., 2019 [34] Mice, normal MMF YES

  1. Different fecal microbiota composition in the MMF group wih dominant bacteria represented, at the class level, by Clostridia, Bacteroidia, and Bacilli after 8 days of treatment and further expansion with continued MMF expansion of Gammaproteobacteria, Erysipelotrichia, and, to a lesser extent, Deltaproteobacteria classes

  2. Higher abundance in the MMF group of Bacteroides vulgatus, Bacteroides fragilis, Bacteroides caccae, Bacteroides uniformis, Bacteroides ovatus, and Bacteroides nordii
Tourret et al., 2017 [66] Mice, normal PRED
TAC
MMF
EVERO
PRED + TAC + MMF 		YES
  • (1)

    FECAL MICROBIOTA: Higher β-diversity in the PRED group. Higher abundance, in the PRED group, at the phylum level, of Firmicutes. Lower abundance in the PRED group at the phylum level, of Bacteroidetes, and, at the order level, of Bacteroidales. Variable, unreproducble effects with other cIMDs

  • (2)

    ILEAL MICROBIOTA: depletion of the Clostridium genus in the groups PRED andPRED + TAC + MMF
Wang et al., 2021 [67] Mice, SLE (MRL/lpr mice) PRED YES

  1. Higher α-diversity with PRED

  2. Higher abundance, in the PRED group, at phylum level, of Proteobacteria, and, at genus level, of Parasutterella and Enterorhabdus genus

  3. Lower abundance, in the PRED group, of Rikenella, Christensenella, Ruminococcus, and Intestinimonas
Xu et al., 2020 [68] Mice, EAE SIR YES
  • (1)

    α-Diversity was decreased in EAE and normalized by SIR

  • (2)

    Different composition of fecal microbiota with or without SIR

  • (3)

    Most abundant bacteria in the control group: Bacteroidia, Bacteroidetes, Burkholderiales, Sutterella, Anaerolinaceae.T78, Turicibacteraceae, Turicibacterales, Turicibacter and Bifidobacterium

  • (4)

    Most abundant bacteria in the EAE group: Bacteroides, Bacteroidaceae, Rikenellaceae, Dorea, Mycoplasmataceae and Mycoplasmatales

  • (5)

    Most abundant bacterial spp in the SIR group: Firmicutes, Oscillospira, Bacteroidales, Allobaculum, Anaerotruncus, Rikenellaceae.AF12, Odoribacteraceae, Odoribacter, Rikenella and Streptococcus
Zhang et al., 2018 [69] Mice, ST TAC YES

  1. No difference in α-diversity

  2. Higher abundance in the TAC group of Allobaculum, Bacteroides, and Lactobacillus

  3. Lower abundance in the TAC group of Clostridium, Ruminococcus, Rikenella, Ruminococcaceae, and Oscillospira
Zhang et al., 2021 [70] Rat, normal PRED YES

  1. No difference in α-diversity

  2. Lower abundance in thePRED group, at the phylum level, of Spirochaetes, at the family level, of Lachnospiraceae, Spirochaetaceae, Desulfovibrionaceae, and Rikenellaceae and at genus level, of Eisenbergiella, Alistipes, and Clostridium XIVb

  3. Higher abundance in the PRED group, at the family level, of Porphyromonadaceae, and at the genus level of Anaerobacterium

Abbreviations: ABX: antibiotics; AIP: autoimmune pancreatitis; HSCT: hemopoietic stem cell transplantation; CD: Crohn’s disease; CyA: cyclosporin A; DIO: diet-induced obesity; EAE: experimental autoimmune encephalomyelitis; EAU: experimental autoimmune uveitis; EVERO: everolimus; KT: kidney transplantation; LT: liver transplantation; MMF, mycophenolate mofetil; PRED: prednisone; PREDN: prednisolone; SHR: spontaneous hypertensive rats; SIR: sirolimus; ST: skin transplantation; TAC: tacrolimus; TM: transverse myelitis.