Table 4.
References | N and study design |
Supplement/
comparator |
Intervention ingredient/s and supplement duration | Outcome measure/s (Δ in mean/median from pre- to post-supplementation period unless otherwise indicated) |
---|---|---|---|---|
Intestinal permeability | ||||
Russo et al. (62) |
N = 20 Study design: RXT |
Prebiotic vs. placebo | Inulin-enriched pasta, 5 wk | Urinary lactulose/mannitol ratio: Int ↓ 0.02, Pla ↔ 0.00 (p < 0.05). Serum zonulin: Int ↓ 1.61 ng/ml, Pla ↑ 0.35 ng/ml (p < 0.05). Fecal zonulin: Int ↑ 0.01 μg/g, Pla ↔ 0.00 μg/gNS |
Axelrod et al. (63) |
n = 7 RXT |
Probiotic vs. placebo | L. salivarius UCC118, 4 wk | Fecal zonulin: Int ↓ 0.18 mg/dL, Pla ↓ 0.2 mg/dL NS |
Lamprecht et al. (76) |
n = 23 RCT |
Probiotic vs. placebo | B. bifidum W23, B lactis W51, E. faecium W54, L. acidophilus W22, L. brevis W63, L. lactis W58, 14 wk | Fecal zonulin: Int ↓ 8.8 ng/ml, Pla ↑ 1.6 ng/ml (p = 0.019) |
Townsend et al. (88) |
n = 25 RCT |
Probiotic vs. placebo | Bacillis subtilis DE111, 12 wk | Serum zonulin: Int ↑ 0.2 ng/ml, Pla ↑ 0.2 ng/mlNS |
Roberts et al. (94) |
n = 20 RCT |
Synbiotic vs. prebiotic | L. acidophilus CUL-60 (NCIMB 30157), L. acidophillus CUL-21 (NCIMB 30156), B. bifidum CUL-20 (NCIMB 30172), B. animalis subspecies lactis CUL-34 (NCIMB 30153, Fructooligosaccharides, 12 wk | Urinary lactulose/mannitol ratio: Int ↑ 0.011, Pla ↑ 0.029NS |
West et al. (98) |
n = 22 RCT |
Synbiotic vs. prebiotic |
L. paracasei subs Paracasei (L. casei 431®), B. animalis ssp. lactis (BB-12®), L. acidophilus LA-5, L. rhamnosus GG, Raftiline, Raftilose GR, 3 wk |
Lactulose/mannitol ratio: NSbetween groups (data not reported) |
Endotoxin responses | ||||
Burton et al. (66) |
n = 13 RXT |
Probiotic vs. placebo | S. thermophilus, L. delbrueckii spp. Bulgaricus, L. rhamnosus GG, 2 wk | LPS: Int ↓ 0.3 pg/ml, Pla ↓ 0.05 pg/mlNS |
Gill et al. (68) |
n = 8 RXT |
Probiotic vs. placebo |
L. casei, 1.0 × 1011 cells/bottle Commercial supplement, taken twice daily for 7 days |
Gram negative endotoxin: Int ↑ 0.1 EU/ml, Pla ↑ 0.3 EU/mlNS |
Carbuhn et al. (67) |
n = 17 RCT |
Probiotic vs. placebo | B. longum 35624, 6 wk | LPS: NSbetween groups (data not reported) LBP: NSbetween groups (data not reported) |
Roberts et al. (94) |
n = 20 RCT |
Synbiotic vs. placebo | L. acidophilus CUL-60 (NCIMB 30157), L. acidophillus CUL-21 (NCIMB 30156), B. bifidum CUL-20, B. animalis subspecies lactis CUL-34 (NCIMB 30153), Fructooligosaccharides, 12 wk | Endotoxin units: Int ↓ 2.30 pg/ml, Pla ↓ 0.84 pg/ml NS IgG endotoxin antibodies (anti-LPS): Int ↑ 42 MU/ml, Pla ↓ 42 MU/mlNS |
Cytokine responses | ||||
Axelrod et al. (63) |
n = 7 RXT |
Probiotic vs. placebo | L. salivarius UCC118, 4 wk | IL-6: (ΔΔ pre to post-exercise, pre to post-intervention) Int ↑ 0.5 pg./ml, Pla: ↑ 1.4pg/mlNS |
Batatinha et al. (65) | n = 27 | Probiotic vs. placebo |
B. animalis. Lactis 10 × 109; L. Acidophilus 10 × 109
1 sachet daily for 30 days |
IL-10: (baseline to pre-ex Δ) Int: ↓ 5.5 ng/ml, Pla: ↓ 3.2 ng/mlNS IL-4: Int: ↓ 3.0 ng/ml, Pla: ↓ 0.9 ng/mlNS IL-6: Int: ↔ 0 ng/ml, Pla: ↓ 2.5 ng/mlNS IL-2: Int: ↓ 0.4 ng/ml, Pla: ↓ 2.6 ng/mlNS IL-15: Int: ↓ 0.4 ng/ml, Pla: ↓ 0.6 ng/mlNS IL-8 (ng/ml): Int: ↑ 0.4 ng/ml, Pla: ↓ 3.8 ng/mlNS IL-1β: Int: ↓ 0.7 ng/ml, Pla: ↓ 0.8 ng/mlNS TNF-α: Int: ↓ 2.2 ng/ml, Pla: ↓ 3.7 ng/mlNS IFN-γ : Int: ↓ 2.6 ng/ml, Pla: ↓ 9.0 ng/mlNS |
Burton et al. (66) |
n = 13 RXT |
Probiotic vs. placebo | S. thermophilus, L. delbrueckii spp. Bulgaricus, L. rhamnosus GG, 2 wk | TNF-α: Int ↑ 0.75 pg/ml, Pla ↑ 0.95 pg/mlNS IL-6: Int ↓ 0.45 pg/ml, Pla ↑ 0.65 pg/mlNS CCL2: Int ↑ 1.8 pg/ml, Pla ↑ 12.55 pg/ml (p = 0.01) CCL5: Int ↓ 12.75 pg/ml, Pla ↓ 7.6 pg/mlNS |
Carbuhn et al. (67) |
n = 17 RCT |
Probiotic vs. placebo | B. longum 35624, 6 wk | IL-1ra: Int ↓ 107 pg/ml, Pla ↓ 37 pg/mlNS IFN-γ, IL-1B, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, IL-17F, and IL-22, TNF-α_ were below detectable levels in assay. |
Gill et al. (68) |
n = 8 RXT |
Probiotic vs. placebo | L. casei, 1 wk | IL-6: Int ↑ 0.1 pg/ml, Pla ↑ 0.4 pg/mlNS IL-1β: Int ↓ 0.05 pg/ml, Pla ↓ 0.02 pg/mlNS TNF-α: Int ↓ 0.1 pg/ml, Pla ↑ 0.2 pg/mlNS IFN-γ: Int ↑ 0.1 pg/ml, Pla ↑ 0.7 pg/mlNS IL-10: Int ↑ 1.2 pg/ml, Pla ↑ 4.8 pg/mlNS IL-8: Int ↔ 0.0 pg/ml, Pla ↑ 0.3 pg/mlNS |
Hoffman et al. (73) |
n = 15 RCT |
Probiotic vs. placebo | Inactivated Bacillus coagulans; 2 wk | IFN-γ : Int: ↓ 0.2 pg/ml, Pla: ↓ 3.6 pg/mlNS
IL-10 : Int: ↑ 0.4 pg/ml, Pla: ↓ 1.4 pg/mlNS IL1-B: Int: ↑ 0.3 pg/ml, Pla: ↑ 2.8 pg/mlNS IL-2: Int: ↓ 0.3 pg/ml, Pla: ↓ 0.3 pg/mlNS IL-6: Int: ↓ 0.2 pg/ml, Pla: ↓ 1.0 pg/mlNS IL-8: Int: ↓ 2.4 pg/ml, Pla: ↓ 3.6 pg/mlNS TNF-α: Int: ↓ 1.7 pg/ml, Pla: ↓ 4.5 pg/mlNS |
Lamprecht et al. (76) |
n = 23 RCT |
Probiotic vs. placebo | B. bifidum W23, B lactis W51, E. faecium W54, L. acidophilus W22, L. brevis W63, L. lactis W58, 14 wk | TNF-α: Int ↓ 17.1 pg/ml, Pla ↑ 4.7 pg/mlNS IL-6: Int ↓ 1.0 pg/ml, Pla ↑ 0.1 pg/mlNS |
Schreiber et al. (82) |
n = 27 RCT |
Probiotic vs. placebo |
L. helveticus Lafti L10, B. animalis ssp. lactis Lafti B94 E. faecium R0026, B. longum R0175 Bacillus subtilis R0179, 90 days |
ANCOVA, (Δ) changes from baseline, adj. for training loads. IL-6 adj: Int: 0.11 ± 0.64, Pla: −0.25 ± 0.6NS TNF-α adj: Int: −0.02 ± 0.23, Pla: 0.06 ± 0.21NS CRP adj: Int: 443.82 ± 238.73, Pla: 231.55 ± 381.28NS |
Smarkusz-Zarzecka et al. (83) |
n = 66 RCT |
Probiotic vs. placebo |
B. lactis W52, L. brevis W63, L. casei W56, Lactococcus lactis W19, Lactococcus lactis W58, L. acidophilus W37, B. bifidum W23, L. salivarius W24. 3 months |
CRP: Male: Δ: Int: ↓0.12 mg/L, Pla: ↓ 0.31 mg/LNS
Female Δ: Int: ↓1.3 mg/L, Pla: ↓ 0.6 mg/LNS TNF-α: Male: Δ: Int: ↓ 1.62 mg/L, Pla: ↓ 0.88 mg/LNS Female: Δ: Int: ↓ 1.43 mg/L, Pla: ↓1.72 mg/LNS |
Tavares-Silva et al. (87) |
n = 14 RCT |
Probiotic vs. placebo | Gelatinous capsules: Lactobacillus acidophilus-LB-G80, Lactobacillus paracasei-LPc-G110, Lactococcus subp. lactis-LLL-G25, Bifidobacterium animalis subp. lactis-BL-G101, Bifidobacterium bifidum-BB-G90; 30 days | IL-2 (Baseline to 24 h before marathon) Int: ↓ 0.37 pg/ml (p < 0.04), Pla: ↓ 0.2 pg/mlNS IL-4 (Baseline to 24 h before marathon) Int: ↓ 0.73 pg/mlNS, Pla: ↓ 0.89 pg/ml (p < 0.04) IL-10 (Baseline to 24 h before marathon) Int: ↓ 0.97 pg/ml (p < 0.001), Pla: ↓ 0.05 pg/mlNS TNF-α (Baseline to 24 h before marathon) Int: ↑ 0.09 pg/mlNS, Pla: ↓0.05 pg/mlNS |
Townsend et al. (88) |
n = 25 RCT |
Probiotic vs. placebo | Bacillis subtilis DE111, 12 wk | TNF-α: Int: Δ: ↓ 0.25 pg/ml, Pla: Δ: ↑ 0.36 pg/ml Int ↓ Pla, p = 0.024 IL-10: Int: Δ: ↑ 0.1 pg/ml, Pla Δ: ↑ 0.15 pg/mlNS |
Vaisberg et al. (89) |
n = 42 RCT |
Probiotic vs. placebo | L. casei Shirota, 30 days | IL-1β: Int ↑ 22.7 pg/ml, Pla ↑ 20.9 pg/mlNS
IL-1ra: Int ↑ 16.3 pg/ml, Pla ↑ 10.5 pg/mlNS IL-4: Int ↑ 9.4 pg/ml, Pla ↑ 11.3 pg/mlNS IL-5: Int ↑ 7.2 pg/ml, Pla ↑ 6.7 pg/mlNS IL-6: Int ↑ 4.4 pg/ml, Pla ↑ 0.9 pg/mlNS IL-10: Int ↑ 5.7 pg/ml, Pla ↑ 2.6 pg/mlNS IL-12p70: Int ↑ 6.9 pg/ml, Pla ↑ 3.6 pg/mlNS IL-13: Int ↑ 7.3 pg/ml, Pla ↑ 6.9 pg/mlNS TNF-α: Int ↑6.6 pg/ml, Pla ↑ 22.2 pg/mLNS |
Quero et al. (93) |
n = 27 RCT |
Synbiotic vs. placebo | B. lactis CBP-001010, L. rhamnosus CNCM I-4036, B. longum ES1, Fructooligosaccharides, 30 days | IL-1β: Sedentary: Int: ↑ 0.3 pg/mL (p < 0.01), Pla: ↑ 0.1 pg/mLNS
Athletes: Int: ↓ 0.2 pg/mLNS, Pla: ↓ 0.2 pg/mLNS IL-10 Sedentary: Int: ↓ 0.3 pg/mL (p < 0.01), Pla: ↓ 0.4 pg/mL (p < 0.05) Athletes: Int: ↑ 0.05 pg/mLNS, Pla: ↓ 0.05 pg/mLNS |
West et al. (98) |
n = 22 RCT |
Synbiotic vs. prebiotic |
L. paracasei subs Paracasei (L. casei 431®), B. animalis ssp. lactis (BB-12®), L. acidophilus LA-5, L. rhamnosus GG, Raftiline, Raftilose GR, 3 wk |
IL-16: 50% greater increase in Pre vs. Syn (p = 0.02) IL-18: NSbetween pre and syn, no additional data shown IL-12 and IFN-γ: Undetectable in assay |
Gastrointestinal function | ||||
Damen et al. (55) |
n = 27 RXT |
Prebiotic vs. placebo | Arabinoxylan oligosaccharides (AXOS), 3 wk | Defecation frequency: Int ↓ 0.1/day, Pla ↑ 0.1/day (p < 0.05) Bristol stool form scale: Int ↓ 0.1/day, Pla ↑ 0.2/dayNS |
Kleessen et al. (59) |
n = 45 RCT |
Prebiotic vs. prebiotic vs. placebo | Chicory inulin (CH) or Jerusalem artichoke inulin (JA), 3 wk | Defecation frequency: CH ↑ 3/wk (p < 0.05), JA ↑ 2/wk (p < 0.05), Pla ↑ 2/wk (p < 0.05) Stool consistency (1–4 scale, hard to soft): CH: ↑ 2 (p < 0.05), JA: ↑ 3 (p < 0.05), Pla: ↑ 1NS |
Russo et al. (61) |
n = 20 RXT |
Prebiotic vs. placebo | Inulin-enriched pasta, 5 wk | Ultrasound full gastric emptying time: Int ↑ 30 min (p < 0.05), Pla ↔ 0 minNS Electrogastrography (% normal slow waves): Pre-Prandial: Int ↑ 12.5%, Pla ↑ 6.5% (p = 0.05) Post-prandial: Int ↑ 5.6%, Pla ↑ 2.0% (p = 0.03) |
Russo et al. (45) |
n = 20 RXT |
Prebiotic vs. placebo | Inulin-enriched pasta, 5 wk | Ultrasound half gastric emptying time: Int ↑ 8.3 min (p < 0.05), Pla ↑ 1.4 minNS |
Reimer et al. (60) |
N = 48 RXT |
Prebiotic vs. Prebiotic vs. placebo | Chicory inulin type fructans (ITF), 4 wk | Stools/d (Δ c/f baseline): Int 1: −0.1 ± 0.2, Con 1: 0.3 ± 0.2NS
Int 2: −0.1 ± 0.2, Con 2: 0 ± 0.1NS Bristol Stool Rating [(1–7) Δ c/f baseline]: Int 1: −0.1 ± 0.3, Con 1: −0.4 ± 0.3NS Int 2: −0.1 ± 0.3, Con 2: 0 ± 0.3NS |
Bacterial taxa | ||||
Damen et al. (55) |
n = 27 RXT |
Prebiotic vs. placebo | Arabinoxylan oligosaccharides (AXOS), 3 wk | FISH analysis to count number of different bacterial groups. Total bacteria cell counts were determined by 4′-6-diamidino-2-phenylindole. NSChanges in abundance or diversity between groups or pre-post supplementation in the same group |
Finegold et al. (56) |
n = 32 RCT |
Prebiotic vs. Prebiotic vs. placebo | Xylooligosaccharides (XOS), 8 wk | Bacterial diversity (Operational Taxonotic Units, species level and Shannon index): NSin α-diversity (OTU) or Shannon index. 16S rRNA gene sequencing/log10 scale of bacterial counts (CFU/g) ↑Bifidobacterium count in high dose XOS only (p < 0.05) ↑Bacteroides fragilis in high dose XOS only (p < 0.05) ↑ total anaerobes count in high dose XOS only (p < 0.05) NSFor total aerobes, Lactobacillus, Enterobacteriaceae, and Clostridium counts cf. baseline in all groups ↓Enterobacteriaceae count cf placebo after washout (p < 0.05) |
François et al. (57) |
n = 63 RXT |
Prebiotic vs. Prebiotic vs. placebo | Arabinoxylan oligosaccharides (AXOS), 3 wk | FISH analysis to count number of different bacterial groups. Total bacteria cell counts were determined by 4'-6-diamidino-2-phenylindole. Percentage of bifidobacterial calculated as the ratio of the absolute amounts of bifidobacteria to the total bacterial cell count. Bifidobacteria (log10 counts/g dry weight feces): High: 9.3, Low: 9.0, Pla: 8.9 High vs. Low p < 0.05 High vs. Pla p < 0.001NS for Lactobacilli, Faecalibacterium prausnitzii, Clostridium histolyticum–lituseburense or Roseburia–Eubacterium rectale |
Kleessen et al. (59) |
n = 45 RCT |
Prebiotic vs. prebiotic vs. placebo | Chicory inulin (CH) or Jerusalem artichoke inulin (JA), 3 wk | Bacterial counts were assessed by fluorescent in situ hybridization or colony forming units, as assessed by conventional culture methods. |
All data expressed in log10 counts/g wet weight feces
Total bacteria: CH: ↑ 0.1, JA: ↔0, Pla: ↔0, NSClostridium coccoides/Eubacterium rectale cluster : CH: ↓ 0.6 (p < 0.05), JA: ↓ 0.6 (p < 0.05), Pla: ↓0.3, NSBacteroides/Prevotella: CH: ↓ 0.4 (p < 0.05), JA: ↓ 0.6 (p < 0.05), Pla: ↑ 0.1 CH and JA both > Pla (p < 0.05) Faecalibacterium prausnitzii: CH: ↓ 0.2, JA: ↓ 0.2, Pla: ↓ 0.1, NSBifidobacterium: CH: ↑ 1.2, JA: ↑ 1.2, Pla: ↑ 0.3 CH and JA both > Pla (p < 0.05) Atopobium group: CH:↔ 0, JA: ↓ 0.2, Pla: ↔ 0, NSLactobacillus: CH: ↓ 0.9, JA: ↓ 0.5, Pla: ↓ 0.7, NSEnterococcus: CH: ↓ 0.9, JA: ↓ 0.4, Pla: ↑ 0.4, NSEnterobacteriaceae: CH: ↓ 0.4, JA: ↓ 0.9, Pla: ↓ 0.7NS |
||||
Reimer et al. (60) |
n = 48 RXT |
Prebiotic vs. Prebiotic vs. placebo | Chicory inulin type fructans (ITF), 4 wk | Results are expressed as relative abundance (%) of Bifidobacterium per total bacteria (Bifidobacterium 16S rRNA gene copies × 100/total 16S rRNA gene copies). Bacterial diversity NSin α-diversity. Community Structure NS in β-diversity Microbial abundance (phylum) (Con = > Int 1/Int 1 = > Con) Actinobacteria: Con: 6.02 ± 5.26 Int 1: 15.23 ± 12.37, ↑ 153% p < 0.01(adj) Int: 11.70 ± 8.65 Con: 6.36 ± 3.95 ↓ 83% p < 0.01(< adj) Firmicutes Con: 85.91 ± 9.02 Int 1: 78.72 ± 10.96, ↓ 8% p < 0.01(adj) Int: 82.52 ± 9.58 Con: 88.13 ± 4.37 ↑ 6% p < 0.01(adj) Bacteroidetes Con: 6.51 ± 7.96 Int 1: 3.48 ± 4.26, ↓ 46% p = 0.05(adj) (Con = > Int 2/Int 2 = > Con) Actinobacteria Con: 8.07 ± 7.38 Int 2: 13.19 ± 12.37 0.01 ↑ 63% NSProteobacteria Con: 0.79 ± 1.29 Int 2: 0.38 ± 0.39 0.04 ↓ 51%NS Family (Con ≥ Int 1/Int 1 ≥ Con) Bifidobacteriaceae Con: 2.52 ± 2.90 Int 1: 10.28 ± 9.09, p < 0.01(adj) ↑ 308% p < 0.01(adj) 7.57 ± 8.08 2.63 ± 1.88 ↓ 65% p < 0.01(adj) |
Actinomycetaceae Con: 0.06 ± 0.09 Int 1: 0.24 ± 0.29 ↑ 300% p < 0.01(adj) Int 1: 0.23 ± 0.24 Con: 0.09 ± 0.08 ↑ 60% p < 0.01(adj) Microbacteriaceae Con: 0.003 ± 0.01 Int 1: 0.01 ± 0.02 ↑ 233% p < 0.01(adj) Int 1: 0.01 ± 0.02 0.0006 ± 0.003 ↓ 94% p < 0.05(adj) Cellulomonadaceae Con: 0.0003 ± 0.002 Int 1: 0.01 ± 0.01 ↑ 3,233% p < 0.01(adj) Micrococcaceae Con: 0.06 ± 0.10 Int 1: 0.19 ± 0.33 ↑ 216% p < 0.01(adj) Brevibacteriaceae Con: 0.01 ± 0.03 Int 1: 0.03 ± 0.05 ↑ 200% p < 0.01(adj) Family (Con ≥ Int 2/Int 2 ≥ Con) Micrococcaceae Con: 1.18 ± 1.72 Int 2: 2.37 ± 2.67 ↑ 101%NS |
||||
Vibrionaceae Con: 0.21 ± 0.44 Int 2: 0.05 ± 0.08 ↓ 76%NS Bifidobacteriaceae Con: 1.17 ± 1.91 Int 2: 2.39 ± 3.63 ↑ 104%NS Enterobacteriaceae Con: 0.42 ± 0.93 Int 2: 0.10 ± 0.17 ↓ 76NS Actinomycetaceae Con: 0.44 ± 0.77 Int 2: 0.88 ± 1.44 ↑ 100%NS Genus (Con ≥ Int 1/Int 1 ≥ Con) Bifidobacterium Con: 5.30 ± 5.87 Int 1: 18.73 ± 14.99, ↑ 253% p < 0.01(adj) Int 1: 11.91 ± 12.02 Con: 4.63 ± 3.42 ↓ 61% p < 0.01(adj) Actinomyces Con: 0.13 ± 0.18 Int 1: 0.45 ± 0.49, ↑ 246% p < 0.01(adj) Int 1: 0.37 ± 0.38 Con: 0.16 ± 0.15 ↓ 56% p < 0.02(adj) Cellulomonas Con: 0.0007 ± 0.01 Int 1: 0.01 ± 0.03 ↑ 1,328% p < 0.02(adj) Nesterenkonia Con: 0.12 ± 0.21 Int 1: 0.35 ± 0.54 ↑ 191% p < 0.03(adj) Lachnospira Con: 2.20 ± 2.70 Int 1: 0.93 ± 1.36 ↓ 57% p < 0.04(adj) Oscillospira Con: 1.11 ± 1.01 Int 1: 0.65 ± 0.54 ↓ 41% p < 0.04(adj) Brevibacterium Con: 0.03 ± 0.05 Int 1: 0.06 ± 0.08 ↑ 100% p < 0.04(adj) Genus (Con = > Int 2) Nesterenkonia Con: 2.46 ± 3.32 Int 2: 4.86 ± 4.75 ↑ 97% NS Vibrio Con: 0.50 ± 1.12 Int 2: 0.10 ± 0.16 ↓ 80% NS Bifidobacterium Con: 2.47 ± 3.83 Int 2: 4.62 ± 6.13 ↑ 87%NS Actinomyces Con: 0.91 ± 1.53 Int 2: 1.67 ± 2.46 ↑ 83%NS |
||||
Axelrod et al. (63) |
n = 7 RXT |
Probiotic vs. placebo | L. salivarius UCC118, 4 wk | DNA extraction by shotgun metagenomic sequencing. Shannon and Simpson index NSin α-diversity or richness. Probiotic data only, no placebo data available Phyla: Verrucomicrobia ↓ 0.144% (q = 0.001) Genus: Prosthecobacter ↓ 0.141% (q = 0.004) Species: fusiformis ↓ 0.051% (q = 0.006) |
Burton et al. (66) |
n = 13 RXT |
Probiotic vs. placebo |
S. thermophilus, L. delbrueckii spp. Bulgaricus, L. rhamnosus GG, 2 wk |
16S rRNA gene sequencing Relative abundance compared to baseline S. salivarius spp. thermophilus: Int ↑ 0.10%, Pla ↔ 0.0% (p < 0.05) L. delbrueckii spp. Bulgaricus: Int ↑ 0.02%, Pla ↔ 0.0% (p < 0.05) L. rhamnosus GG: Int ↔ 0.0%, Pla ↔ 0.0% NS Bilophila wadsworthia: Int ↓ 0.07%, Pla ↓ 0.27% NS B. kashiwanohense/B. pseudocatenulatum: Int ↓ 0.05%, Pla ↑ 0.05% (p < 0.05) |
Huang et al. (74) |
n = 20 male RCT |
Probiotic vs. placebo | L. plantarum PS128, 4 wk | 16S rRNA gene sequencing No baseline data reported. % Relative abundance (Phyla) Int: Fermicutes 46.6%, Bacteriodetes 47.0%, Proteobacteria 3.8%, Actinobacteria 2.1%, Fusobacteria 0.3% Pla: Fermicutes 50.3%, Bacteriodetes 41.6%, Proteobacteria 4.9%, Actinobacteria 1.0%, Fusobacteria 1.5% NS between groups. Relative abundance (Genus) Anaerotruncus (× 10−4) Int 0, Pla 1.0; Caproiciproducens (× 10−4) Int 0.1, Pla 1.0; Coprobacillus (× 10−5) Int 0, Pla 3.3; Desulfovibrio (× 10−5), Int 0, Pla 5.9; Dielma (× 10−5), Int 0, Pla 2.6; Family_XIII_UCG_001 (× 10−5), Int 0.9, Pla 9.2; Holdemania (× 10−5), Int 0.6, Pla 7.2; Oxalobacter (× 10−5), Int 0, Pla 6.1; Int < Pla (p < 0.05) Akkermansia (× 10−3), Int 5.0, Pla 1.3; Bifidobacterium (× 10−2), Int 1.5, Pla 0.8; Butyricimonas (× 10−3), Int 4.7, Pla 2.3; Lactobacillus (× 10−3), Int 1.7, Pla 0.7; Int > Pla (p < 0.05) |
Klein et al. (75) |
n = 26 RXT |
Probiotic vs. placebo | B. lactis 420x, L. acidophilus 74-2, 5 wk | Preparation of fecal samples by FISH analysis. Relative abundance compared to baseline B. lactis: Int ↑ 1.43%, Pla ↑ 0.39% (p < 0.05) L. acidophilus: Int ↑ 0.18%, Pla ↑ 0.02% (p < 0.05) |
Lee et al. (77) |
n = 16 RCT |
Probiotic vs. placebo |
L. paracasei DSM 32785 (LPC12), L. rhamnosus DSM 32786 (LRH10), L. helveticus DSM 32787 (LH43), L. fermentum DSM 32784 (LF26), and S. thermophilus DSM 32788 (ST30)
28 days |
qPCR method was used for the identification and quantification of gut microbiota. Pre-post Δ in Log10 cells/g Lactobacillus: Int: ↑ 0.2, Pla: ↑ 0.5, NS Bifidobacterium: Int: ↓ 0.2, Pla: ↑ 0.3 “Decreased in intervention group” (p < 0.05) Clostridium: Int: ↓ 1.0, Pla:↓ 1.0 NS Bacteroides: Int: ↓ 0.3, Pla: ↑ 0.1 NS |
Lin et al. (78) | n = 21 | Probiotic vs. placebo | Bifidobacterium longum subsp. Longum, 5 wk | 16S rRNA gene sequencing Phylum: Int: Actinobacteria and Firmicutes greater abundance post-supplementation, compared with Pla. (p-value not shown). Proteobacteria reduced abundance post-supplementation, compared with Pla. (p-value not shown). Genus: Int: ↑ Bifidobacterium compared with Pla (p = 0.0027). 9-fold ↑ in Lactobacillus count. Species: Bifidobacterium longum subsp. longum relative abundance Int: 0.95%; ↑ 8.63-fold (p = 0.0178). Pla: 0.11% NS in amounts of common strains |
Sánchez Macarro et al. (80) |
n = 43 RCT |
Bifidobacterium longum CECT 7347 Lactobacillus casei CECT 9104, and Lactobacillus rhamnosus CECT 8361 6 wk | 16S rRNA gene sequencing Bacterial diversity Richness: Int:↔ 0, Pla: ↓6 NS Simpson index: Int: ↔ 0, Pla: ↑0.03, NS Shannon index: Int: ↑0.01, Pla: ↑0.15 NS Family (log relative counts) Rhodospirillaceae: Int < Pla, log2 fold = 2.71, p = 0.019 (adj) Streptococcaceae: Int < Pla, log2 fold = 2.20, p = 0.019(adj) Genera (log relative counts) Rhodospirillum: Pla > Int, p = 0.007(adj) Streptococcus: Pla > Int, p = 0.007(adj) Within group differences noted in genera. |
|
Son et al. (84) |
n = 15 RCT |
Probiotic vs. placebo | L. acidophilus, L. casei, L. helveticus, B. bifidum, 60 days | 16S rRNA gene sequencing Shannon and Simpson index NS in α-diversity, pre and post Species: NS changes in the abundance of the four microorganisms present (three Lactobacilli and one Bifidobacterium). |
West et al. (90) |
n = 88 RCT |
Probiotic vs. placebo | Lactobacillus fermentum VRI-003 PCC®, 11 wk | Microbiome Diversity (16SrRNA) NS changes in bacterial diversity (data not shown) All data reported as raw bacterial counts—no statistical testing of between group changes. Total bacteria: Males: Int ↓ 0.5 × 1010, Pla Pre: ↓ 0.5 × 1010 Females: Int ↑ 0.7 × 1010, Pla ↓ 1.0 × 1010 C. coccoides: Males: Int ↓ 2.3 × 108, Pla ↓ 3.4 × 108 Females: Int ↔ 0, Pla ↓ 1.54 × 109 E. coli: Males: Int ↑ 6.4 × 105, Pla ↑ 6.8 × 105 Females: Int ↑ 1.36 × 107, Pla ↑ 4.3 × 104 Bifibacteria: Males: Int ↓ 0.3 × 107, Pla ↓ 5.6 × 106 Females: Int ↑ 0.7 × 106, Pla ↓ 6.1 × 106 Bacteroides: Males: Int ↑ 0.6 × 106, Pla ↑ 1.6 × 106 Females: Int ↑ 1.3 × 106, Pla ↓ 4.4 × 107 Lactobacillus: Males: Int ↑ 5.8 × 104, Pla ↓ 2.8 × 106 Females: Int ↑ 7.0 × 104, Pla ↑ 6.9 × 104 |
Coman et al. (92) |
n = 10 RCT |
Synbiotic vs. placebo | L. rhamnosus IMC 501[R], L. paracasei IMC 502[R], plus oat bran fiber, 4 wk | qPCR procedure for quantification of selected bacterial groups Log CFU/g feces Bacteroides-Prev.-Porphyr. spp.: Int ↓ 0.18 log CFU/g, Pla ↑ 0.21 log CFU/g NS Staphylococcus spp.: Int ↓ 0.08 log CFU/g, Pla ↑ 0.16 log CFU/g NS Cl. coccoides-Eubact. rectale group: Int: ↓ 0.33 log CFU/g, Pla ↓ 0.01 log CFU/g NS Lactobacillus spp.: Int: ↑ 1.44 log CFU/g (p < 0.05), Pla ↓ 0.43 log CFU/g NS Bifidobacterium spp.: Int: ↑ 1.52 log CFU/g (p < 0.05), Pla ↑ 0.16 log CFU/g NS Enterobacteriaceae: Int: ↓ 0.14 log CFU/g, Pla ↑ 0.35 log CFU/g NS |
Valle et al. (96) |
n = 65 RCT |
Synbiotic vs. placebo |
Lactobacillus acidophilus LA-5; Bifidobacterium animalis BB-12
2.3 g of inulin, 30 days |
16S gene sequencing α–Diversity (Shannon index): Int:↓ 0.125 Pla: ↑0.027 NS α–Diversity (Simpson index): Int: ↓0.017, Pla: ↑0.01 NS |
West et al. (98) |
n = 22 RCT |
Synbiotic vs. prebiotic |
L. paracasei subs Paracasei
(L. casei 431®), B. animalis ssp lactis (BB-12®), L. acidophilus LA-5, L. rhamnosus GG, Raftiline, Raftilose GR, 3 wk |
Microbiome Diversity (16SrRNA)
NS changes in bacterial diversity (data not shown) All data reported as raw bacterial counts. Total bacteria: Syn ↔ 0, NS, Pre ↑ 2 × 108 Total Lactobacillus (mean): Syn ↔ 0, Pre ↑ 1.5 × 104 NS L. paracasei (mean): Syn ↑ 8 × 102, Pre ↓ 2 × 102 (“large” 9-fold difference) B. lactis (mean): Syn ↑ 2.7 × 104, Pre ↑ 4.8 × 103NS |
Short chain fatty acids | ||||
Damen et al. (55) |
n = 27 RXT |
Prebiotic vs. placebo | Arabinoxylan oligosaccharides (AXOS), 3 wk |
All data reported in μmol/g wet feces
Total SCFA: Int: ↑ 25.3 (p < 0.05), Pla ↑ 9.6 NS Acetic acid: Int: ↑ 10.2, Pla ↑ 4.8NS Butyric acid: Int: ↑ 7.6 (p < 0.05), Pla ↑ 2.3NS Propionic acid: Int: ↑ 3.2, Pla ↑ 1.3NS |
Finegold et al. (56) |
n = 32 RCT |
Prebiotic vs. Prebiotic vs. placebo | High and Low dose Xylooligosaccharides (XOS), 8 wk | Total SCFA (μmol/g dry feces): High ↓ 0.01, Low ↓ 0.06, Pla ↓ 0.06NS |
François et al. (57) |
n = 63 RXT |
Prebiotic vs. Prebiotic vs. placebo | Arabinoxylan oligosaccharides (AXOS), 3 wk |
All data reported in μmol/g dry feces
Total SCFA: High vs. Pla: ↑ 53.1 (p = 0.001), Low vs. Pla: ↑ 7.8 NS Acetic acid: High vs. Pla: ↑ 38.5 (p = 0.003), Low vs. Pla: ↑ 8.9 NS Butyric acid: High vs. Pla: ↑ 5.0 (p = 0.05), Low vs. Pla: ↓ 3.9 NS Propionic acid: High vs. Pla: ↑ 9.7 (p = 0.003), Low vs. Pla: ↑ 2.9 NS |
Kleessen et al. (59) |
n = 45 RCT |
Prebiotic vs. prebiotic vs. placebo | Chicory inulin (CH) or Jerusalem artichoke inulin (JA), 3 wk | Total SCFA post-intervention (μmol/g wet feces): CH: 142.4, JA: 135.2, Pla: 138.8 NS |
Reimer et al. (60) |
n = 48 RXT |
Prebiotic vs. Prebiotic vs. placebo | Chicory inulin type fructans (ITF), 4 wk | Fecal acetate Int 1: ↑ 2.9 umol/g, Con 1: ↑ 6.7 umol/g NS Int 2: ↑ 6.7 umol/g, Con 2: ↑ 9.2 umol/g NS Fecal proprionate Int 1: ↑ 3.8 umol/g, Con 1: ↑ 2.4 umol/g NS Int 2: ↓ 1.3 umol/g, Con 2: ↑ 1.3 umol/g NS Fecal butyrate Int 1: ↑ 2.5 umol/g, Con 1: ↑ 0.3 umol/g NS Int 2: ↑ 4.4 umol/g, Con 2: ↑ 6.7 umol/g NS Fecal Isobutyrate Int 1: ↔ 0 umol/g, Con 1: ↑ 0.6 umol/g NS Int 2: ↔ 0 umol/g, Con 2: ↔ 0 umol/g NS Fecal Isovalerate Int 1: ↔ 0 umol/g, Con 1: ↔ 0 umol/g NS Int 2: ↔ 0 umol/g, Con 2: ↑ 0.4 umol/g NS |
Huang et al. (74) |
n = 20 male RCT |
Probiotic vs. placebo | L. plantarum PS128, 4 wk | Acetic acid (mean, post only): Int: 4.7 ng/ml, Pla: 3.8 ng/ml Int > Pla (p < 0.05) Proprionic acid (mean, post only): Int: 1.18 ng/ml, Pla: 0.5 ng/ml Int > Pla (p < 0.05) Butyric acid (mean, post only): Int: 0.5 ng/ml, Pla: 0.3 ng/ml Int > Pla (p < 0.05) Decanoic acid (mean, post only): Int: 0.005 ng/ml, Pla: 0.002 ng/ml NS Heptanoic acid (mean, post only): Int: 0.6 ug/ml, Pla: 0.4 ug/ml NS Hexanoic acid (mean, post only): Int: 1.7 ug/ml, Pla: 4.0 ug/ml NS Isobutyric acid (mean, post only): Int: 0.050 ng/ml, Pla: 0.052 ng/ml NS Isovaleric acid (mean, post only): Int: 0.03 ng/ml, Pla: 0.04 ng/ml NS Octanoic acid (mean, post only): Int: 1.1 ug/ml, Pla: 0.7 ug/ml NS Valeric acid (mean, post only): Int: 0.07 ng/ml, Pla: 0.07 ng/ml NS |
Son et al. (84) |
n = 15 RCT |
Probiotic vs. placebo | L. acidophilus, L. casei, L. helveticus, B. bifidum, 60 days | Acetic acid Int: ↓ 40 umol/g, Pla: ↓ 85 umol/g NS Buytric acid Int: ↓ 142 umol/g, Pla: ↑ 125 umol/g Int > Pla at baseline (p-value not shown) Propionic acid Int: ↓ 1.31 umol/g, Pla: ↓ 1.51 umol/g NS |
Klein et al. (75) |
n = 26 RXT |
Probiotic vs. placebo | B. lactis 420 × , L. acidophilus 74-2, 5 wk |
All data post-intervention concentration (μmol/g feces)
Total SCFAs: Int 85.0 μmol/g, Pla 88.5 μmol/g NS Acetic acid Int: 46.7 μmol/g, Pla 49.5 μmol/g NS i-Butyric acid Int 1.9 μmol/g, Pla 2.0 μmol/g NS n-Butyric acid Int 14.6 μmol/g, Pla 15.1 μmol/g NS Propionic acid Int: 16.7 μmol/g, Pla 16.9 μmol/g NS Valeric acid: Int: 2.1 μmol/g, Pla 2.0 μmol/g NS Isovaleric acid: Int: 2.3 μmol/g, Pla 2.4 μmol/g NS Caproic acid: Int: 0.7 μmol/g, Pla 0.6 μmol/g NS |
Valle et al. (96) | n = 65 | Synbiotic vs. placebo |
Lactobacillus acidophilus LA-5; Bifidobacterium animalis BB-12
2.3 g of inulin, 30 days |
Fecal acetate (mmol/L): Int: OR 0.34, 95%CI −0.06, 0.74 Pla: OR 0.16, 95%CI −0.25, 0.57 NS between groups |
Fecal proprionate (mmol/L): Int: OR 0.20, 95%CI −0.01, 0.41 Pla: OR 0·31, 95%CI −0.02, 0.63 NS between groups Fecal butyrate (mmol/L): Int: OR 0.39, 95%CI 0.20, 0.59 Pla: OR 0.25, 95%CI −0.03, 0.47 NS between groups Fecal ammonia (mmol/l): Pla: OR 0.09, 95%CI 0.01, 0.17 Int: OR 0.11, 95%CI 0.04, 0.18 NS between groups |
||||
West et al. (98) |
n = 22 RCT |
Synbiotic vs. prebiotic | L. paracasei subs Paracasei (L. casei 431®), B. animalis ssp. lactis (BB-12®), L. acidophilus LA-5, L. rhamnosus GG, Raftiline, Raftilose GR, 3 wk |
All data reported in μmol/g feces
Acetic acid: Syn ↓ 2, Pre ↓ 6 NS Butyric acid: Syn ↓ 2, Pre ↓ 3 NS Propionic acid: Syn ↓ 2, Pre ↓ 1.5 NS |
Gastrointestinal symptoms | ||||
Damen et al. (55) |
n = 27 RXT |
Prebiotic vs. placebo | Arabinoxylan oligosaccharides (AXOS), 3 wk | GIS: Insufficient incidence to analyze abdominal pain or bloating. Flatulence: Int: NS difference pre-to-post Pla: ↑ 0.53 on 0–4 scale pre-to-post (P = 0.02) |
Finegold et al. (56) |
n = 32 RCT |
Prebiotic vs. Prebiotic vs. placebo | Xylooligosaccharides (XOS), 8 wk |
Symptoms rated from 0 (no symptoms) to 3 (severe)
Excess flatus: High ↑ 0.27, Low ↑ 0.26, ↑ Pla 0.19 NS Borborygmi: High ↑ 0.26, Low ↑ 0.11, ↑ Pla 0.02 NS Bloating: High ↑ 0.28, Low ↑ 0.22, ↑ Pla 0.06 NS Abdominal pain: High ↓ 0.01, Low ↑ 0.27, ↑ Pla 0.10 NS |
François et al. (57) |
n = 63 RXT |
Prebiotic vs. Prebiotic vs. placebo | Arabinoxylan oligosaccharides (AXOS), 3 wk | ↑ Occurrence frequency + ↑ Distress severity, flatulence only cf Pla (P = 0·02) Flatulence (mild/moderate/very disturbing symptoms, %): High 27/7/2, Low 16/7/2, Pla 11/6/2 NS NS all other symptoms. |
Kleessen et al. (59) |
n = 45 RCT |
Prebiotic vs. prebiotic vs. placebo | Chicory inulin (CH) or Jerusalem artichoke inulin (JA), 3 wk |
All data reported as incidence (%) post-supplementation
Flatulence: CH 87, JA 93, Pla 47 (CH and JA > Pla, p < 0.05) Abdominal bloating: CH: 0, JA: 27, Pla: 27 NS Abdominal pain or cramps: CH: 20, JA: 7, Pla: 7 NS Bowel Rumbling: CH: 13, JA: 13, Pla: 13 NS Bowel Cramps: CH: 20, JA: 20, Pla: 13 NS |
Reimer et al. (60) |
n = 48 RXT |
Prebiotic vs. Prebiotic vs. placebo | Chicory inulin type fructans (ITF), 4 wk | Abdominal pain, 0–4 Int 1: 0.3 ± 0.2, Con 1: 0.3 ± 0.2 NS Int 2: 0.4 ± 0.2, Con 2: 0.3 ± 0.2 NS Distension/bloating (0–4) Int 1: 0.5 ± 0.3, Con 1: 0.4 ± 0.2 (P = 0.025) Int 2: 0.6 ± 0.2 (P = 0.023), Con 2: 0.2 ± 0.1 (P = 0.048) NS between groups Flatulence (0–4) Int 1: 0.3 ± 0.2, Con 1: 0.3 ± 0.2 NS Int 2: 0.3 ± 0.2, Con 2: 0.0 ± 0.2 NS Stomach rumbling (0–4) Int 1: 0.1 ± 0.2, Con 1: 0.1 ± 0.2 NS Int 2: 0.2 ± 0.2, Con 2: 0.1 ± 0.1 NS |
Russo et al. (45) |
n = 20 RXT |
Prebiotic vs. placebo | Inulin-enriched pasta, 5 wk | NSDifferences and no major symptoms (data not reported) |
Gleeson et al. (70) |
n = 58 RCT |
Probiotic vs. placebo | L. casei Shirota, 16 wk | GIS Incidence: Int 54%, Pla 57% NS Proportion of days with GIS: Int 2%, Pla 3% (p = 0.008) |
Severity Score: Int 9, Placebo 12 NS Symptom duration (days): Int 4.2, Pla 5.9 NS |
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Haywood et al. (72) |
n = 30 RCT |
Probiotic vs. placebo | L. gasseri, B. bifidum, B. longum, 4 wk | GIS Incidence: Int: 13%, Pla: 13% NS |
Pugh et al. (79) | n = 24 | Probiotic vs. placebo | L. acidophilus CUL60, L. acidophilus CUL21, B. bifidum CUL20, B. animalis subsp. Lactis CUL34, 4 wk | Number of GI scores ≥ 4: Days 1–14: Int 4, Pla 5NS
Days 15–28: Int 2, Pla 11 NS |
Schreiber et al. (82) |
n = 27 RCT |
Probiotic vs. placebo |
L. helveticus Lafti L10, B. animalis ssp. lactis Lafti B94 E. faecium R0026, B. longum R0175 Bacillus subtilis R0179, 90 days |
GIS incidence at rest (ΔGI): Int: −30 ± 48%, Pla: −27 ± 47% NS Categorized as: Nausea incidence at rest (ΔGI): Int −16 ± 43%, Pla: 71 ± 119% Int < Pla, P = 0.01, d = 0.9 Belching incidence at rest (ΔGI): Int: −14 ± 53%, Pla: 62 ± 115%, Int < Pla, P = 0.04, d = 1 Vomiting incidence at rest (ΔGI): Int: −7 ± 30%, Pla: 49 ± 114%, Int < Pla, P = 0.04, d = 0.7 Other sub-categories not reported. |
Strasser et al. (85) |
n = 29 RCT |
Probiotic vs. placebo |
Bifidobacterium bifidum W23 Bifidobacterium lactis W51 Enterococcus faecium W54 Lactobacillus acidophilus W22 Lactobacillus brevis W63 Lactococcus lactis W58 12 wk |
Incidence: “Only one participant in the placebo group experienced GI-discomfort symptoms during the study period.” |
West et al. (90) |
n = 88 RCT |
Probiotic vs. placebo | Lactobacillus fermentum VRI-003 PCC®, 11 wk | No. of GIS episodes: Male: Int 1.01, Pla: 0.49 (Likely ↑) Female: Int 1.44, Pla 0.48, (Likely ↑) Duration of GIS episodes (days): Male: Int 3.3, Pla 1.3, (Likely ↑) Female: Int 3.9, Pla 2.1, (Possible ↑) GIS severity (1–3 scale): Male: Int 1.31, Pla 1.78 (Possible ↓) Female: Int 1.44, Pla 1.75 (Possible ↓) Symptom Load (severity-days): Male: Int 4.4, Pla 2.5 (Possible ↑) Female: Int 5.2, Pla 2.9 (Possible ↑) |
Coman et al. (92) |
n = 10 RCT |
Synbiotic vs. placebo | L. rhamnosus IMC 501[R], L. paracasei IMC 502[R], oat bran fiber, 4 wk |
Data reported as change from baseline, Likert scale (0–5)
Intestinal regularity: Int ↑ 2.6, Pla ↑ 1.8 (p < 0.05) Stool volume: Int ↑ 1.8, Pla ↑ 2.2NS Ease at defecation: Int ↑ 2.2, Pla ↑ 0.6 (p < 0.05) Bloating: Int ↑ 0.2, Pla ↑ 0.4NS Abdominal pain: Int ↔ 0.0, Pla ↓ 0.2NS Intestinal cramps: Int ↔ 0.0, Pla ↓ 0.4NS |
Roberts et al. (94) |
n = 20 RCT |
Synbiotic vs. placebo | L. acidophilus CUL-60 (NCIMB 30157), L. acidophillus CUL-21 (NCIMB 30156), B. bifidum CUL-20, B. animalis subspecies lactis CUL-34 (NCIMB 30153), Fructooligosaccharides, 12 wk | Mean total GIS score during supplemental period: Int 7.00, Pla 13.9 (p < 0.001) Mean GIS severity score during supplemental period: Int 8.00, Pla 16.7 (p < 0.001) |
Valle et al. (96) | n = 65 | Synbiotic vs. placebo |
Lactobacillus acidophilus LA-5; Bifidobacterium animalis BB-12
2·3 g of inulin, 30 days |
Sum of symptoms (nausea, vomiting, diarrhea, abdominal pain, flatulence, loss of appetite, burning and dysphagia) Int: Δ Post-supp.: OR −2·24, 95%CI −3·15, −1·34 Pla: Δ Post-supp: OR −1·16, 95%CI −2·51, 0·18 NSBetween groups. |
CFU, colony forming units; CRP, c-reactive protein; FISH, fluorescence in situ hybridization; GIS, Gastrointestinal symptoms; IFN, interferon; IL, interleukin; Int, Intervention; LBP, lipopolysaccharide binding protein; LPS, lipopolysaccharide; NS, Not significant; OTU, operational taxonomy units; Pla, Placebo; Pre, Prebiotic intervention; RCT, Randomized control trial; RXT, Randomized crossover trial; Syn, Synbiotic intervention; wk, weeks.