Table 1.
Studies investigating the gut microbiome alterations in multiple sclerosis patients.
| Study | Country | Study Design | Profiling Method | Main Results |
|---|---|---|---|---|
| Cantarel et al., 2015 [6] | USA | 5 RRMS/8 HV Stools |
16S rRNA-DNA chip hybridization | β diversity: NA, α diversity: NA Up: Ruminococcus Down: Faecalibacterium, Bacteroides |
| Miyake et al., 2015 [5] | Japan | 20 RRMS/40 HV Stools |
16S rRNA V1–V2 (pyrosequencing) | β diversity: p < 0.05 α diversity: NS up: Streptococcus, Eggerthella down: Faecalibacterium, Prevotella, Anaerostipes |
| Jangi et al., 2016 [44] | USA | 60 RRMS/43 HV Stools |
16S rRNA V3–V5 | β diversity: NS, α diversity: NS Up: Akkermansia, Methanobrevibacter Down: Butyricimonas, Collinsella, Slackia, Prevotella |
| Chen et al., 2016 [45] | USA | 31 RRMS/36 HV Stools |
16S rRNA V3–V5 | β diversity: p < 0.001, α diversity: NS Up: Pseudomonas, Mycoplana, Haemophilus, Blautia, and Dorea Down: Parabacteroides, Adlercreutzia and Prevotella |
| Tremlett et al., 2016 [46] | USA | 18 RRMS/17 HV (pediadric) Stools |
16S rRNA V4 | β diversity: NS, α diversity: NS Up: Desulfovibrionaceae (Bilophila, Desulfovibrio and Christensenellaceae) Down: Lachnospiraceae and Ruminococcaceae |
| Cree et al., 2016 [47] | USA | 16 RRMS/16 HV Stools |
DNA hybridization PhyloChip G3–entire 16S rRNA | NS |
| Swidsinski et al., 2017 [48] | Germany | 25 RRMS/14 HV Stools |
FISH to specific 16S rRNA probes | β diversity: p < 0.001, α diversity: NS, decreased bacterial mass Down: Roseburia, Bacteroides, Faecalibacterium prausnitzii |
| Cosorich et al., 2017 [49] | Italy | 19 RRMS/17 HV Small intestine biopsies |
16S rRNA V3–V5 | β diversity: NA, α diversity: NS Up: Firmicutes/bacteroides ratio, Streptococcus, Down: Prevotella |
| Cekanaviciute et al., 2017 [50] | USA | 71 RRMS/71 HV Stools |
16S rRNA V4 | β diversity: NS, α diversity: NS Up: Akkermansia, Acinetobacter, calcoaceticus Down: Parabacteroides |
| Berer et al., 2017 [51] | Germany | 34 twin pairs (MS/HV) 3 CIS, 22 RRMS, 7 SPMS, 2 PPMS Stools |
16S rRNA V3–V5 + shotgun sequencing |
β diversity: NS, α diversity: NS Up: Akkermansia |
| resella et al., 2017 [52] | Italy | 20 RRMS, 2 diets (10 Western/10 high-fiber diet) Stools |
16S rRNA V4 | α, β diversity: NS Up Lachnospiraceae Coprococcus eutactus, Ruminococcus lactaris, Roseburia intestinalis, Hungatella Down: Th17, correlation Lachnospiraceae, and Treg |
| Tankou et al., 2018 [53] | USA | 9 RRMS/13 HV Stools |
16S rRNA V4 | Probiotics decreased Akkermansia and Blautia, increased Lactobacillus in MS |
| Cignarella et al., 2018 [54] | USA | 8 RRMS before/after intermittent fasting Stools |
16S rRNA V1–V3 | Adiponectin levels correlate with Faecalibacterium |
| Abdurasulova et al., 2018 [55] | Russia | 17 RRMS GA/17 RRMS FG Stools |
16S rRNA | α, β diversity: NA Up: atypical E coli, Enterobacter sp. with GA treatment Down: normal E coli |
| Forbes et al., 2018 [56] | Canada | 19RRMS, 21RA, 20CD, 19UC, 23HV | 16S rRNA V4 | β diversity: NA α diversity: NS Up: Actinomyces, Eggerthella, Anaerofustis, Clostridia XIII, Clostridium III, Faecalicoccus, Streptococcus Down: Butyricicoccus, Faecalibacterium, Dialister, Gemmiger, Lachnospiraceae, Subdolibacterium MS signature partially overlays other inflammatory disease signatures |
| Nourbakhsh et al., 2018 [57] | USA | Pediatric cohort | 16S rRNA V4 | Same cohort than Tremlett et al., 2016 |
| Tankou et al., 2018 [58] | USA | RRMS/HV | 16S rRNA V4 | Same cohort than Tankou et al., Ann Neurol 2018 |
| Tankou et al., 2018 [53] | USA | 9 RRMS (2+GA) 13HV Before and after VSL3 probiotics Stools | 16S rRNA V4 | Up with VSL3: Lactobacillus Down with VSL3: Akkermansia, Blautia Decrease in inflammatory monocytes markers of cell activation |
| Zeng et al., 2019 [59] | China | 34 RRMS/34 NMO/12HV Stools |
16S rRNA V3–V4 + metabolomic |
β diversity: p < 0.01, α diversity: NS Up: Streptococcus Down: Prevotella, Faecalibacterium + Decreased SCFA in MS and NMO |
| Oezguen et al., 2019 [60] | USA | 13 RRMS/14 HV Stools |
16S rRNA V3–V5 | β diversity: NA, α diversity: up p = 0.04 Down: Prevotella |
| Storm-Larsen et al., 2019 [61] | Norway | 27 RRMS +DMF, 9 RRMS +GA or IFN-𝛽 before and after treatment 165 HV Stools |
16S rRNA V3–V4 | β Diversity: p = 0.01, α diversity: NS At baseline in MS vs. HV: Down: Faecalibacterium Up: Faecalibacterium with DMF treatment |
| Kozhieva et al., 2019 [62] | Russia | 15 PPMS/15 HV Stools |
16S rRNA V3–V4 | β diversity: NA, α diversity: increased richness, p < 0.05 Up: Gemmiger, Ruminococcus |
| Ventura et al., 2019 [63] | USA | 40 RRMS/41 HV Stools Multiethnic ancestry |
16S rRNA V4 + shotgun sequencing (24 RRMS/24 HV) |
β diversity: p < 0.01 in Hispanic ancestry α diversity: NS Up: Clostridium in all ancestries, Akkermansia in European ancestry Down: Prevotella in Hispanic ancestry |
| Katz Sand et al., 2019 [64] | USA | 75 untreated RRMS 33 + DMF 60 + GA Stools |
16S rRNA V4 | β diversity: NS, α diversity: NS Up: Lachnospiraceae and Veillonellaceae with all treatments Down: Firmicutes, Fusobacteria, Clostridiales with DMF |
| Choileáin et al., 2020 [65] | USA | 26 RRMS/39 HV Stools |
16s rRNA V4 | β diversity: p < 0.01, α diversity: down (Shannon, p < 0.05) Up: Bacteroidetes Down: Coprococcus, Firmicutes, Paraprevotella, Ruminococcaceae |
| Saresella et al., 2020 [66] | Italy | 26 RRMS/12 SPMS/38 HV Stools |
16S rRNA V3–V4 + metabolomic |
β diversity: p < 0.0001, α diversity: NS Up: Akkermansia in SPMS, Streptococcus in RRMS, Collinsella in RR and SPMS. Serum caproic acid Down: Coprococcus, Roseburia in RR and SPMS, Lachnospira in RRMS. Serum butyric acid |
| Takewaki et al., 2020 [67] | Japan | 62 RRMS/15 SPMS/22 “atypical” MS/20 NMO/55HV Stools |
16S rRNA V1–V2 | β diversity: RRMS, SPMS and NMO vs. HV: p < 0.05 α diversity: NS Up: Akkermansia in RRMS vs. HV. Streptococcus, Clostridium in RRMS and SPMS vs. HV Down: Eubacterium, Lachnospiraceae, Megamonas in RRMS vs. HV |
| Engen et al., 2020 [68] | USA | 1 RRMS before and after FMT Stools |
Shotgun sequencing | β diversity: NA α diversity: FMT increased alpha diversity indices. Up: FMT increased Faecalibacterium Prausnitzii |
| The iMSMS Consortium, 2020 [69] | International | 128 MS/128 HV Household paired Stools |
16S rRNA and Shotgun sequencing | Emphasize the importance of paired household design to reduce interindividual variability |
| Ling et al., 2020 [70] | China | 22 RRMS/33 HV Stools |
16S rRNA V3–V4 | β diversity: NS, α diversity: NS Up: Blautia, Flavonifractor Down: Faecalibacterium, Granulicatella, Prevotella, Roseburia |
| Reynders et al., 2020 [71] | Belgium | 24 untreated RRMS/26 PPMS/20 benign MS, 24, INF𝛽 treated/4 RRMS relapse/120HV Stools |
16S rRNA V3–V4 | β diversity: NA, α diversity: Down in IFN β treated and relapse RRMS compared to benign forms Up: Alistipes, Anaerotruncus, Clostridium cluster IV, Lactobacillus, Methanobrevibacter, Olsenella, Parabacteroides, Ruminococcus, Sporobacter in MS vs. HC Down: Butyricicoccus, Gemmiger, Intestinibacter, Roseburia in MS vs. HC, Butyricicoccus in PPMS vs. RRMS |
| -Cox et al., 2021 [72] | 199 RRMS/44 progressive MS/40 HV Stools |
16S rRNA V4 | β diversity: p < 0.01 RRMS vs. HV, p < 0.01 PPMS vs. HV α diversity: increased Shannon and richness in RR and PPMS compared to HV Up: Clostridium, Bacteroides, Gemella, Akkermansia in RR and progressive MS Down: Prevotella in RRMS, Dorea in RR and progressive MS |
|
| Sterlin et al., 2021 [73] | 30 RRMS/15 CIS/32 HV Stools |
16S rRNA V3–V5 | β diversity: NA, α diversity: NS Commensal-specific gut IgA responses are drastically reduced in MS patients with severe disease |
|
| Jenkins et al., 2021 [74] | 50 RRMS parasite challenge, 24 treated with antiparasitic agent 26 untreated | 16S rRNA V3–V4 | Up: Parabacteroides in treated RRMS Down: Roseburia, Dorea, Tyzzerella, Anaerostipes, and Agathobacter in treated RRMS compared to placebo RRMS No relapse in treated group |
|
| Levi et al., 2021 [75] | 129 RRMS/58 HV Stools |
Shotgun sequencing | β diversity: NA, α diversity: NA Up: Lawsonella Down: Faecalibacterium prausnitzii, Bacteroides fragiils, Eubacterium rectale, Butyrivibrio, Clostridium, Coprococcus, Roseburia |
|
| Castillo-Álvarez et al., 2021 [76] | Europe (Spain) | 15 RRMS IfNb/untreated 15RRMS/14 HV Stools |
16S rRNA V4 | β diversity: NS, α diversity: down (p = 0.08) Up: Faecalibacterium, Ruminococcus, Blautia, Anaerostipes, Bifidobacterium Down: Prevotella IFN β partially restored microbiota |
FISH: fluorescence in situ hybridization, NS: non-significant, NA: not available, DMF: dimethyl fumarate, FG: fingolimod, IFNβ: interferon-β, GA: glatiramer acetate, RA: rheumatoid arthritis, CD: Crohn’s disease, UC: ulcerative colitis, FMT: fecal microbiota transplant.