Limosilactobacillus reuteri DSM 17938 and PTA 6475 as adjunct in Helicobacter pylori therapy: Systematic review and meta-analysis

Table 1 Characteristics of the randomized controlled trials included in the meta-analysis

Ref.	Country	Number of patients ITT and PP (Exp/Con)	Age (years)	Eradication regimen	Reuteri regimen	Diagnostic methods for H. pylori infection
						Diagnosis	Eradication
Moreno Márquez et al[17]	Spain	80 (40/40); 68 (35/33)	18-65	For 10 days pylera plus omeprazole 2-times a day	For 30 days, L. reuteri DSM 17938 and ATCC PTA 6475 tablets	Histology or UBT or stool antigen test	UBT
Dore et al[18]	Italy	46 (23/23); 40 (21/19)	Over 18	For 10 days tetracycline and metronidazole plus rabeprazole. One regimen was supplemented with pylera, 2 cps bis in die	For 27 days, L. reuteri DSM 17938 and ATCC PTA 6475 tablets, twice daily	UBT and/or stool antigen test	UBT and/or stool antigen test
Dore et al[19]	Italy	99 (49/50); 92 (46/46)	Over 18	For 10 days tetracycline and metronidazole plus pantoprazole. One regimen was supplemented with pylera, 2 cps bis in die	For 10 days, L. reuteri DSM 17938 and ATCC PTA 6475 tablets, twice daily	Histology and/or UBT or stool antigen test	UBT or stool antigen test
Emara et al[20]	Egypt	70 (35/35); 70 (35/35)	18-60	For 14 days triple therapy	For 28 days, L. reuteri DSM 17938 and ATCC PTA 6475 tablets	Histology, rapid urease test and stool antigen test	Histology, rapid urease test and stool antigen test
Francavilla et al[21]	Italy	40 (20/20); 40 (20/20)	35-68	Sequential therapy	For 28 days, L. reuteri ATCC 55730 tablets, once daily	Histology, rapid urease test, UBT, stool antigen test	UBT
Francavilla et al[22]	Italy	100 (50/50); 86 (43/43)	Over 18	For 7 days triple therapy	For 96 days, L. reuteri DSM 17938 and ATCC PTA 6475 tablets, once daily	Histology, rapid urease test or UBT	UBT
Kotzev et al[23]	Bulgaria	55 (26/29); 20 (11/9)	18-70	Sequential therapy	For 28 days, L. reuteri DSM 17938 and ATCC PTA 6475 tablets, once daily	Histology, rapid urease test, UBT, stool antigen test	UBT, stool antigen test
Lionetti et al[24]	Italy	40 (20/20); 40 (20/20)	3-18	Sequential therapy	For 20 days, L. reuteri ATCC 55730 tablets, once daily	Histology, rapid urease test, UBT	UBT
Ojetti et al[25]	Italy	90 (45/45); 90 (45/45)	18-65	For 7 days triple therapy1	For 14 days, L. reuteri ATCC 55730 tablets, one tablet three times a day	UBT	UBT
Poonyam et al[26]-a	Thailand	50 (25/25); 50 (25/25)	Over 18	For 7 days, bismuth subsalicylate twice daily, metronidazole 3-times a day, tetracycline 4-times a day, and dexlansoprazole 60 mg twice daily	For 7 days, L. reuteri DSM 17938 and ATCC PTA 6475 tablets, twice daily	Histology, rapid urease test	UBT
Poonyam et al[26]-b	Thailand	50 (25/25); 50 (25/25)	Over 18	For 14 days bismuth subsalicylate twice daily, metronidazole 3-times a day, tetracycline 4-times a day, and dexlansoprazole 60 mg twice daily	For 14 days, L. reuteri DSM 17938 and ATCC PTA 6475 tablets, twice daily	Histology, rapid urease test	UBT
Shahraki et al[27]	Iran	50 (25/25); 50 (25/25)	5-14	For 14 days triple therapy with 30 days omeprazole	For 28 days, L. reuteri DSM 17938 tablets, once daily	Histology	UBT
Scaccianoce et al[28]	Italy	33 (17/16); 32 (17/15)	Over 18	For 7 days triple therapy	For 7 days L. reuteri ATCC 55730 tablets, twice daily	Histology	UBT

¹Levofloxacin-based triple therapy: Proton pump inhibitor, levofloxacin, and amoxicillin. Standard triple therapy: Proton pump inhibitor, clarithromycin, and amoxicillin.

The table summarizes the country of origin, sample size (intention-to-treat and per-protocol populations), patient age range, eradication regimens, Limosilactobacillus reuteri supplementation protocols, and the diagnostic methods used for the detection of Helicobacter pylori at baseline and for confirming eradication. Different strains of Limosilactobacillus reuteri (DSM 17938, ATCC PTA 6475, and ATCC 55730) and various durations of supplementation were employed across studies. Triple therapy: Proton pump inhibitors-clarithromycin-amoxicillin. Sequential therapy: Proton pump inhibitors plus amoxicillin for 5 days, proton pump inhibitors plus clarithromycin plus tinidazole for the next 5 days. ITT: Intention to treat; PP: Per protocol; Exp: Experimental group; Con: Control group; H. pylori: Helicobacter pylori; L. reuteri: Limosilactobacillus reuteri; UBT: Urea breath test.

Table 2 Gastrointestinal side effects associated with Helicobacter pylori eradication therapy: Comparison between groups treated with and without Limosilactobacillus reuteri supplementation

Adverse event	RR (95%CI)	I2 (%)	P value for heterogeneity	Comment
Vomiting	0.94 (0.60-1.47)	0.0	0.652	No difference between groups
Epigastric pain	0.51 (0.22-1.19)	32.4	0.228	Trend in favor of L. reuteri
Constipation	0.69 (0.32-1.52)	0.0	0.639	No difference between groups
Abdominal pain	0.73 (0.41-1.33)	27.3	0.220	Consistent but non-significant benefit
Asthenia	0.58 (0.18-1.85)	33.1	0.225	Weak trend in favor of L. reuteri
Vertigo	1.00 (0.26-3.78)	0.0	1.000	No difference between groups
Appetite loss	0.50 (0.05-5.31)			Assessed in a single study
Dysgeusia	0.44 (0.24-0.80)	14.4	0.320	56% RR reduction; consistent across 7 comparisons from 6 RCTs
Nausea	0.44 (0.32-0.60)	0.0	0.679	56% RR; high consistency across 4 comparisons from 3 RCTs
Diarrhea	0.34 (0.21-0.55)	0.0	0.752	66% RR reduction; consistent across 5 RCTs
Bloating	0.47 (0.18-1.23)	67.8	0.008	Trend in favor of L. reuteri

Reported are risk ratios with 95% confidence intervals and heterogeneity statistics (I² and P values for heterogeneity). RR: Risk ratio; CI: Confidence interval; RCT: Randomized controlled trial; L. reuteri: Limosilactobacillus reuteri.