Actual concept of "probiotics": Is it more functional to science or business?

Table 1 Results of clinical trials with probiotics in irritable bowel syndrome

Ref.	Patients (n)	Duration of therapy	Probiotic strains	Dose (CFU/d)	Outcomes
Maupas et al[88]	34	1 mo	Saccharomyces boulardii	9 × 109	Improved stool number and consistency
Gade et al[89]	54	1 mo	Paraghurt (Streptococcus faecium)	1 × 10¹²	Improved symptoms
Halpern et al[90]	18	4 mo	Lactobacillus acidophilus	2 × 1010	Improved symptoms
O’Sullivan et al[91]	25	1 mo	Lactobacillus GG	1 × 1010	No benefit
Nobaek et al[92]	60	1 mo	Lactobacillus plantarum 299V Pro-Viva®	5 × 107	Improved global symptoms
Niedzielin et al[93]	40	1 mo	Lactobacillus plantarum 299V Pro-Viva®	2 × 1010	Improved global symptoms
Kim et al[94]	25	2 d-IBS	VSL3®	9 × 10¹¹	Reduced bloating
Tsuchiya et al[95]	68	3 mo	Lactobacillus acidophilus	1.5 × 106	Improved symptoms
			Lactobacillus helveticus	1.3 × 109
			Bifidobacterium	4.95 × 109
O’Mahony et al[96]	80	2 mo	Bifidobacterium longum subspecies infantis vs Lactobacillus salivarius	1 × 1010	B. infantis: improved global symptoms and anti-inflammatory cytokine profileLactobacillus salivarius: no benefit
Kajander et al[97]	103	6 mo	Mixture (2 strains of Lactobacillus rhamnosus, Bifidobacterium breve, Propionibacterium freudenreichii)	8-9 × 109	Improved global symptoms
Bittner et al[98]	25	0.5 mo	29 bacteria + prebiotic Prescript-Assist®	2.6 × 108	Improved wellbeing
Sen et al[99]	12	1 mo	Lactobacillus plantarum 299V Pro-Viva®	5 × 107	No benefit; Study design flawed
Bausserman et al[100]	50	1.5 mo	Lactobacillus GG	2 × 1010	No benefit
Niv et al[101]	39	6 mo	Lactobacillus GG	2 × 108	No benefit Francis severity IBS score
Kim et al[102]	48	1 or 2 mo	VSL3®	8 × 109	Reduced flatulence, retarded colonic transit
Whorwell et al[103]	362	1 mo	Bifidobacterium longum subspecies infantis 35 624 in 3 doses	1 × 106	Improved global symptoms
				1 × 108
				1 × 1010
Long et al[104]	60	0.5 mo	Bifidobacterium	2 × 108	Symptoms resolved
Gawrońska et al[105]	104	1 mo	Lactobacillus GG	6 × 109	Reduced frequency of pain
Moon et al[106]	34	1 mo	Bifidobacterium subtilis, Streptococcus faecium	750 mL/d, CFU/d not given	Reduced frequency pain
Marteau et al[107]	116	1 mo	Lactibiane® (4 strains of Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus lactis, Streptococcus thermophilus)	1 × 1010	Reduced painIncreased colonic transit in those with constipation
Simrén et al[108]	76	1.5 mo	Lactobacillus plantarum 299V	2 × 109	No benefit
Simrén et al[109]	118	2 mo	Lactobacillus paracasei ssp paracasei	2 × 1010	No benefit
Guyonnet et al[110]	274	1.5 mo	Bifidobacterium animalis, Streptococcus thermophilus and Lactobacillus bulgaricus	1.25 × 1010 1.2 × 109	Improved bloating and constipation
Drouault-Holowacz et al[111]	116	1 mo	Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus lactis, Streptococcus thermophilus	1 × 1010	Not significant in relieving symptoms
Sinn et al[112]	40	1 mo	Lactobacillus acidophilus	2 × 108	Improved abdominal pain and discomfort
Enck et al[113]	297	1 mo	Escherichia coli, Enterococcus faecalis	4.5 × 102	Improvement in pain
Hun et al[114]	44	2 mo	Bacillus coagulans	8 × 108	Improvement abdominal pain and bloating
Dolin et al[115]	61	2 mo	Bacillus coagulans	2 × 109	Diminution of diarrhea
Ligaarden et al[116]	16	1 mo	Lactobacillus plantarum	1010/L	Worsening of symptoms
Moayyedi et al[117]	19 randomised controlled trials in 1650 patients				Probiotics appear to be efficacious but the magnitude of benefit and the most effective strains are uncertain

CFU: Colony-forming unit; IBS: Irritable bowel syndrome.

Table 2 Results of clinical trials with probiotics in ulcerative colitis

Ref.	Patients (n)	Duration of therapy	Probiotic strains	Dose (CFU/d)	Outcomes
Kruis et al[118]	120	12 wk	Escherichia coli Nissle 1917	50 × 1010	Maintaining the remission (similar to 5-ASA)
Rembacken et al[119]	116	1 yr	Escherichia coli Nissle 1917	5 × 1010	Induction of remission (similar to 5-ASA); maintaining of relapses (similar to 5-ASA)
Venturi et al[120]	20	1 yr	VSL3®	5 × 10¹¹	Maintaining the remission
Ishikawa et al[121]	21	1 yr	Milk with bifidobacteria	10 × 108	Maintaining the remission
Guslandi et al[122]	25	4 wk	Saccharomyces boulardii	250 mg × 3	Induction of remission
Kruis et al[123]	327	1 yr	Escherichia coli Nissle 1917	2.5-25 × 109	Induction of remission (5-ASA better than probiotic)
Tursi et al[124]	90	8 wk	Balsalazide/VSL3®	900 × 108	Induction of remission
Cui et al[125]	30	8 wk	Bifidobacteria	1.26 g/d	Maintaining of remission
Kato et al[126]	20	12 wk	Bifidobacterium-fermented milk vs placebo	109	CDAI lower in Bifidobacterium fermented milk that in placebo
Furrie et al[127]	18	4 wk	Bifidobacterium longum + prebiotic (Synergy 1)	4 × 10¹¹	Induction of remission
Bibiloni et al[128]	32	6 wk	VSL3®	1800 billion × 2	Induction of remission
Zocco et al[129]	187	12 mo	Lactobacillus GG vs mesalazina	18 × 109	No difference between the treatment groups
Henker et al[130]	34	12 mo	Escherichia coli Nissle 1917	5 × 1010	Maintenance of remission
Miele et al[131]	29	12 mo	VSL3®	450-1800 × 109	Induction of remission (92.8% in treated with VSL3® and 36.4% in the placebo group)
Sood et al[132]	147	12 wk	VSL3®	3.6 × 10¹²	Induction of remission (42.9% against 15.7% in the placebo group)
Matthes et al[133]	57	4 wk	Escherichia coli Nissle 1917	10-40 × 108	Induction of remission
Sang et al[134]	13 RCTs				Heterogenity between the studies in their methodology and results

5-ASA: 5-aminosalicylic acid; CDAI: Crohn's disease activity index; CFU: Colony-forming unit; RCTs: Randomised controlled trials.

Table 3 Results of clinical trials with probiotics in patients with Crohn’s disease

Ref.	Patients (n)	Duration of therapy	Probiotic strains	Dose (CFU/d)	Outcomes
Malchow et al[135]	24	3 mo	Escherichia coli Nissle 1917	2.5 × 1010	Maintaining the remission
Guslandi et al[136]	32	6 mo	Saccharomyces boulardii	1 g	Postsurgical prevention of CD recurrence (relapse rate probiotic+ 5-ASA vs 5-ASA alone)
Prantera et al[137]	45	1 yr	Lactobacillus GG	12 × 109	Postsurgical prevention of CD recurrence (no effects)
Schultz al[138]	11	6 mo	Lactobacillus GG	2 × 109	Probiotics are not superior to placebo in maintaining remission
Bousvaros et al[139]	75	1 yr	Lactobacillus GG	2 × 1010	Probiotics are not superior to placebo in maintaining remission
Marteau et al[140]	98	6 mo	Lactobacillus johnsonii	4 × 109	Postsurgical prevention of CD recurrence (recurrence rate decreased vs placebo)
Chermesh et al[141]	30	24 mo	Synbiotic 2000 (Pediococcus pentoseceus, Lactobacillus raffinolactis, Lactobacillus paracasi susp paracsei, Lactobacillusplantarum 2362) and 4 fermentable fibers vs placebo	10¹¹	Postsurgical prevention of CD recurrence (NS)
Van Gossum et al[142]	70	12 wk	Lactobacillus johnsonii or placebo	1010	Postsurgical prevention of CD recurrence (NS)
Rolfe et al[143]	7 RCTs				No benefit of probiotics in the maintenance of remission of CD
Rahimi et al[144]	8 RCTs				None benefit for probiotic treatment in the maintenance of clinical remission of CD

RCTs: Randomised controlled trials; CD: Crohn's disease; 5-ASA: 5-aminosalicylic acid; CFU: Colony-forming unit; NS: Not significant.

Table 4 Reference studies concerning the probiotic role of bacterial DNA

Ref.	Outcomes
Lammers et al[23]	Bacterial DNA from faeces collected after VSL-3 administration modulated a decrease of IL-1β and an increase of IL-10
Rachmilewitz et al[26]	Study in a mouse IBD model: protective effects of probiotics contained in VSL-3 are mediated by their DNA and TLR9 signaling mediates anti-inflammatory effect
Iliev et al[27]	Lactobacillus rhamnosus GG DNA induces B-cell proliferation and activate DC
Ghadimi et al[28]	Bacterial DNA inhibited IL-4 and IL-5 secretion in different Lactobacilli
Ménard et al[30]	Study from 5 bifidobacterial strains: unmethylated CpG motifs are specific to bacterial DNA by activating TLR9

IL: Interleukin; IBD: Irritable bowel disease; TLR: Toll-like receptor.

Table 5 Reference studies concerning the probiotic role of molecules presented at the bacterial surface

Ref.	Outcomes
Mazmanian et al[33]	Bacterial capsular PSA elaborated by Bacteroides fragilis activates CD4+ and elicits cytokine production
Mazmanian et al[35]	Purified PSA suppress pro-inflammatory IL-17 production and protects from inflammatory disease by induction of IL-10
Ryu et al[36]	Purified LTA from Gram-positive bacteria has lower potency in the stimulation of Toll-like receptor-2 pathway to induce pro-inflammatory molecules.
Grangette et al[37]	Modified LTA is able to induce secretion of anti-inflammatory IL-10
Benz et al[39]	Lipoproteins and glycoproteins at the cell surface are attractive candidates as probiotic molecules
Schlee et al[40]	Flagellins of the Escherichia coli Nissle 1917 induces expression of human β-defensin 2
Matsumoto et al[83]	Purified PSPG-I from Lactobacillus casei Shirota has anti-inflammatory actions in chronic intestinal inflammatory disorders

PSA: Polysaccharide A; IL: Interleukin; LTA: Lipotheichoic acid; PSPG: Polysaccharide-peptidoglycan.