Skip to main content
. 2022 Dec 7;9:1003620. doi: 10.3389/fnut.2022.1003620

Table 4.

Systematic review study outcomes of included studies that attempted to determine the impact of prebiotic, probiotic, and synbiotic supplementation on gastrointestinal outcomes at rest.

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
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.