Association of a probiotic to a Helicobacter pylori eradication regimen does not increase efficacy or decreases the adverse effects of the treatment: a prospective, randomized, double-blind, placebo-controlled study

Abstract Background The treatment for the eradication of Helicobacter pylori (H. pylori) is complex; full effectiveness is rarely achieved and it has many adverse effects. In developing countries, increased resistance to antibiotics and its cost make eradication more difficult. Probiotics can reduce adverse effects and improve the infection treatment efficacy. If the first-line therapy fails a second-line treatment using tetracycline, furazolidone and proton-pump inhibitors has been effective and low cost in Brazil; however it implies in a lot of adverse effects. The aim of this study was to minimize the adverse effects and increase the eradication rate applying the association of a probiotic compound to second-line therapy regimen. Methods Patients with peptic ulcer or functional dyspepsia infected by H. pylori were randomized to treatment with the furazolidone, tetracycline and lansoprazole regimen, twice a day for 7 days. In a double-blind study, patients received placebo or a probiotic compound (Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum and Streptococcus faecium) in capsules, twice a day for 30 days. A symptom questionnaire was administered in day zero, after completion of antibiotic therapy, after the probiotic use and eight weeks after the end of the treatment. Upper digestive endoscopy, histological assessment, rapid urease test and breath test were performed before and eight weeks after eradication treatment. Results One hundred and seven patients were enrolled: 21 men with active probiotic and 19 with placebo plus 34 women with active probiotic and 33 with placebo comprising a total of 55 patients with active probiotic and 52 with placebo. Fifty-one patients had peptic ulcer and 56 were diagnosed as functional dyspepsia. The per-protocol eradication rate with active probiotic was 89.8% and with placebo, 85.1% (p = 0.49); per intention to treat, 81.8% and 79.6%, respectively (p = 0.53). The rate of adverse effects at 7 days with the active probiotic was 59.3% and 71.2% with placebo (p = 0.20). At 30 days, it was 44.9% and 60.4%, respectively (p = 0.08). Conclusions The use of this probiotic compound compared to placebo in the proposed regimen in Brazilian patients with peptic ulcer or functional dyspepsia showed no significant difference in efficacy or adverse effects. Trial registration Current Controlled Trials ISRCTN0471401

Effects of the probiotic Bifidobacterium animalis subsp. lactis on the non-surgical treatment of periodontitis. A histomorphometric, microtomographic and immunohistochemical study in rats.

Lactobacillus probiotics have been investigated in periodontitis. However, the effects of the genus Bifidobacterium on periodontitis are hardly known. This study evaluated the effects of the probiotic (PROB) Bifidobacterium animalis subsp. lactis (B. lactis) HN019 as an adjunct to scaling and root planing (SRP) in rats with experimental periodontitis (EP). At baseline, 32 rats were assigned to 4 groups: C (control), PROB, EP-SRP and EP-SRP-PROB. In groups EP-SRP and EP-SRP-PROB, the mandibular first molars of the animals received a ligature. At day 14, the ligatures were removed and SRP was performed. Animals of groups PROB and EP-SRP-PROB were orally administered with 10 mL/day of 109 colony forming units of B. lactis HN019 for 15 days, starting at day 14. Animals were euthanized at day 29. Histomorphometric, microtomographic and immunohistochemical analyses were performed. Microbiological effects of B. lactis on biofilm were also evaluated. Data were statistically analyzed (ANOVA, Tukey; Kruskal-Wallis, Dunn's; Two-tailed t-test; p<0.05). Group EP-SRP-PROB presented reduced alveolar bone resorption and attachment loss when compared with Group EP-SRP (p<0.05). Group EP-SRP-PROB showed significantly fewer osteoclasts, increased expression of anti-inflammatory cytokines and reduced expression of proinflammatory cytokines compared with Group EP-SRP (p<0.05). B. lactis promoted a higher ratio between aerobic and anaerobic bacteria in biofilm samples (p<0.05). B. lactis HN019 may have a role in the treatment of EP in rats, as an adjunct to SRP

Effects of the probiotic <i>Bifidobacterium animalis subsp</i>. <i>lactis</i> on the non-surgical treatment of periodontitis. A histomorphometric, microtomographic and immunohistochemical study in rats

<div><p><i>Lactobacillus</i> probiotics have been investigated in periodontitis. However, the effects of the genus <i>Bifidobacterium</i> on periodontitis are hardly known. This study evaluated the effects of the probiotic (PROB) <i>Bifidobacterium animalis subsp</i>. <i>lactis</i> (<i>B</i>. <i>lactis</i>) HN019 as an adjunct to scaling and root planing (SRP) in rats with experimental periodontitis (EP). At baseline, 32 rats were assigned to 4 groups: C (control), PROB, EP-SRP and EP-SRP-PROB. In groups EP-SRP and EP-SRP-PROB, the mandibular first molars of the animals received a ligature. At day 14, the ligatures were removed and SRP was performed. Animals of groups PROB and EP-SRP-PROB were orally administered with 10 mL/day of 10⁹ colony forming units of <i>B</i>. <i>lactis</i> HN019 for 15 days, starting at day 14. Animals were euthanized at day 29. Histomorphometric, microtomographic and immunohistochemical analyses were performed. Microbiological effects of <i>B</i>. <i>lactis</i> on biofilm were also evaluated. Data were statistically analyzed (ANOVA, Tukey; Kruskal-Wallis, Dunn’s; Two-tailed t-test; <i>p</i><0.05). Group EP-SRP-PROB presented reduced alveolar bone resorption and attachment loss when compared with Group EP-SRP (<i>p</i><0.05). Group EP-SRP-PROB showed significantly fewer osteoclasts, increased expression of anti-inflammatory cytokines and reduced expression of proinflammatory cytokines compared with Group EP-SRP (<i>p</i><0.05). <i>B</i>. <i>lactis</i> promoted a higher ratio between aerobic and anaerobic bacteria in biofilm samples (<i>p</i><0.05). <i>B</i>. <i>lactis</i> HN019 may have a role in the treatment of EP in rats, as an adjunct to SRP.</p></div

Histomorphometric analysis of periodontal tissues.

<p>Means and standard deviations of ANB (A; furcation area) and AL (B; interproximal area), with comparisons among groups. Photomicrographs of periodontal tissues in the furcation (C-F) and interproximal areas (G-J) of mandibular first molars: Group C (C and G); Group PROB (D and H); Group EP-SRP (E and I); Group EP-SRP-PROB (F and J). Abbreviations and symbols: ab = alveolar bone; ct = connective tissue; pdl = periodontal ligament; ANB = area of no bone; AL = attachment loss; FM = first molar; SM = second molar; black arrows = cementoenamel junction; white arrows = epithelial attachment; * = <i>p</i><0.05; ** = <i>p</i><0.01; *** = <i>p</i><0.001. Scale bars: C-J = 200 μm. (Hematoxylin and Eosin stain).</p

Immunohistochemical analyses—IL-1β and CINC.

<p>Medians, interquartile range and maximum and minimum values of the immunolabeling scores for IL-1β (A) and CINC (B), with comparisons among groups. Photomicrographs showing immunolabeling for IL-1β (C-F) and CINC (G-J) in the furcation regions of mandibular first molars: Group C (C and G); Group PROB (D and H); Group EP-SRP (E and I); Group EP-SRP-PROB (F and J). Abbreviations: ab = alveolar bone; ct = connective tissue; pdl = periodontal ligament; * = <i>p</i><0.05. Scale bars: C-J = 80 μm. (Hematoxylin counterstaining).</p

Immunohistochemical analyses—IL-10 and TGF-β1.

<p>Medians, interquartile range and maximum and minimum values of the immunolabeling scores for IL-10 (A) and TGF-β1 (B), with comparisons among groups. Photomicrographs showing immunolabeling for IL-10 (C-F) and TGF-β1 (G-J) in the furcation regions of mandibular first molars: Group C (C and G); Group PROB (D and H); Group EP-SRP (E and I); Group EP-SRP-PROB (F and J). Abbreviations: ab = alveolar bone; ct = connective tissue; pdl = periodontal ligament; * = <i>p</i><0.05. Scale bars: C-J = 80 μm. (Hematoxylin counterstaining).</p

Histomorphometric analysis of small intestine.

<p>Mean values and standard deviations of VH (A) and CD (B) in intestinal sections, with comparisons among groups. Photomicrographs of small intestine (duodenum sections): Group C (C); Group EP-SRP (D); Group PROB (E); Group EP-SRP-PROB (F). Abbreviations and symbols: LC = crypt of Lieberkühn; VH = villous height; CD = crypt depth; black arrowhead = calciform cells; * = Significant difference (<i>p</i><0.05) when compared with Groups C, EP-SRP and EP-SRP-PROB; ^† = Significant difference (<i>p</i><0.05) between Groups EP-SRP and EP-SRP-PROB; ^‡ = Significant difference (<i>p</i><0.05) between Groups C and EP-SRP-PROB; ^§ = Significant difference (<i>p</i><0.05) between Groups C and EP-SRP. Scale bars: C-F = 50 μm. (Hematoxylin and Eosin stain).</p