Lacticaseibacillus rhamnosus GG DSM 33156 effects on pathogen defence in the upper respiratory tract: a randomised, double-blind, placebo-controlled paediatric trial.

Acute upper respiratory tract infections (URTIs) are caused by numerous viruses and bacteria. URTIs can be a cause of morbidity and are among the most common reasons for visiting healthcare practitioners and prescribing antibiotics to children in addition to causing absenteeism from school and work. Oral intake of Lacticaseibacillus rhamnosus GG DSM 33156 has shown beneficial health effects in several clinical trials, primarily relating to immune function and gastrointestinal health in children and adults. It has also been suggested that oral intake of L. rhamnosus GG DSM 33156 can reduce the incidence rate and alleviate symptoms of URTIs in children. We here report the results of a randomised, double-blind, placebo-controlled trial of 619 children aged 2-6 years conducted at a single centre in Scotland. The children, who were in day care or primary school, were followed over a 16-week intervention period with 309 randomised in the active group and 310 in the placebo group. The parents or guardians reported a daily healthcare status and any presumed episodes of URTI, which were subsequently confirmed by a general practitioner. The investigational product was well tolerated in the trial. Although a general trend towards a beneficial effect was observed, this trial did not demonstrate that L. rhamnosus GG DSM 33156 significantly reduced the incidence of URTIs, diagnosed by a general practitioner according to prespecified criteria (primary endpoint). Moreover, none of the secondary efficacy endpoints were met. Applying a Ward's hierarchical clustering, two separate clusters, focussing on four quality of life-related endpoints, were identified. Cluster 1 was associated with more severe URTI characteristics than cluster 2. Cluster 2 was significantly enriched with children who consumed the product, indicating that the symptoms children experience during an URTI are alleviated by the intake of L. rhamnosus GG DSM 33156. The study is registered at ClinicalTrials.gov ID: NCT03636191.

Effect of probiotic lozenges containing Lactobacillus reuteri on oral wound healing: a pilot study.

It has been suggested that beneficial bacteria may stimulate wound healing. The aim was to investigate the effect of topical applications of probiotic lactobacilli on the healing of standardised oral wounds. This pilot study employed a randomised, placebo-controlled, double-blind cross-over design. Standardised biopsies were punched in the oral mucosa of 10 healthy volunteers, with and without exposure to two strains of Lactobacilli reuteri administrated as lozenges and topical oil. The healing was scored clinically after 2, 5 and 8 days. The amount of exudate was quantified through filter papers and the levels of selected cytokines and chemokines were determined with multiplex immunoassays. Saliva samples were collected before the biopsy and after healing for determination of oxytocin with ELISA. Subjectively perceived pain and discomfort was reported through a daily logbook. There was a clear tendency of improved healing in test group at the 2-and 5-day check-ups but the difference compared with the placebo intervention was not statistically significant (P=0.08). Higher but non-significant expressions of the tumour necrosis factor (TNF) superfamily ligand members 13 (APRIL) and 13B (BAFF), as well as the chemokine interleukin 8 (IL-8), were displayed in wound exudates from the probiotic group as compared with placebo, particularly after 5 and 8 days. The salivary levels of oxytocin were significantly lower (P<0.05) in the placebo group at the 8-day follow-up. The mean number of days with pain and/or discomfort after the biopsies was similar in both groups. No side-effects were reported. The findings of this pilot study justify a larger clinical trial to elucidate the possible role of probiotic supplements on oral wound healing.

Randomized pilot study on probiotic effects on recurrent candidiasis in oral lichen planus patients.

Some patients with oral lichen planus (OLP) experience recurrent oral candidiasis(OC). Probiotic bacteria have shown to reduce the oral Candida count in vivo. OBJECTIVE: To study whether probiotic intervention reduces recurrent OC in patients with OLP. MATERIAL AND METHODS: Twenty-two patients with symptomatic OLP were enrolled in the double-blinded, randomized, placebo-controlled intervention study. Lozenges containing Lactobacilli reuteri (DSM 17938 and ATCC PTA 5289) or placebo were dissolved intra-orally three times daily for 16 weeks, after which patients were followed up for 36 weeks. Mucosal symptoms, VAS pain, OLP severity score, plaque index (PI) and gingival index (GI), Candida count/carriage, and OC and/or need for symptomatic treatment were registered. Statistical significance was set at p < .05. RESULTS: No difference was observed between the groups during the intervention or follow-up in terms of recurrent OC (p = .966) or need for symptomatic treatment (p = 1.000). There was no difference in terms of Candida count (p = .96) or carriage over time (p = .511). GI decreased in the probiotic group and increased in the placebo group (p = .046). OLP severity score decreased in both groups during the study period (p = .039). Across the entire study period, the placebo group had higher VAS pain score (p = .037). CONCLUSIONS: Probiotic intervention did not reduce recurrent OC or Candida count/carriage, but the study experienced recruitment problems, which may have influenced results.

Effect of tablets containing probiotic candidate strains on gingival inflammation and composition of the salivary microbiome: a randomised controlled trial.

The aim of the study was to investigate clinical and microbial effects of probiotic candidate strains in patients with moderate gingivitis. The null hypothesis was that the clinical measurements with treatment would not differ from placebo. 47 adult patients were enrolled in a randomised placebo-controlled trial with a 4-week intervention of tablets containing a mix of Lactobacillus rhamnosus PB01, DSM 14869 and Lactobacillus curvatus EB10, DSM 32307 or placebo. Clinical examinations and samplings were done at baseline and after 2, 4 and 6 weeks. The clinical endpoints were general bleeding on probing (BOP), general plaque index (PI) and flow of gingival crevicular fluid (GCF). In addition, the concentration of selected cytokines (interleukin (IL)-1ß, IL-6, IL-8, IL-10, tumour necrosis factor alpha (TNF-α)) in GCF was determined with multiplex immunoassays. The profiles of the salivary microbiome were analysed with Next Generation Sequencing (NGS) and qPCR. In contrast to the placebo group, there was a significant reduction in BOP and amount of GCF (P<0.05) after 4 weeks in the probiotic test group when compared with baseline. The general PI was less affected although there was a tendency of decreased plaque levels in the probiotic group (P=0.05-0.09). The cytokines were unaffected by the intervention as well as the salivary microbiome. The Shannon index showed no significant differences between the groups or alterations over time. The occurrence of both probiotic strains increased in saliva of the test subjects during the intervention but returned to baseline levels within 2 weeks. Although a marked improvement in gingival health was recorded in the probiotic group, the null hypothesis could not be rejected.

Fluoride varnish or fluoride mouth rinse? A comparative study of two school-based programs.

OBJECTIVE: In many Danish communities, school-based fluoride programs are offered to children with high caries risk in adjunct to tooth brushing. The purpose of this field trial was to compare the caries-preventive effectiveness of two different fluoride programs in 6-12 year olds. BASIC RESEARCH DESIGN: Clinical controlled trial. CLINICAL SETTING: The 2-year study was conducted in Public Dental Clinics in a multicultural low-socioeconomic suburban area of Odense, Denmark with an elevated prevalence of caries compared to the city average. PARTICIPANTS: 1,018 children (aged 6-12 years) from 9 different schools were enrolled after informed consent and their class unit was randomly allocated to one of two fluoride programs. INTERVENTIONS: One group received a semi-annual fluoride varnish applications (FV) and the other group continued with an existing program with fluoride mouth rinses once per week (FMR). All children received oral hygiene instructions and comprehensive dental care at the local Public Dental Clinics throughout the study period. MAIN OUTCOME MEASURES: Increment of caries lesions in permanent teeth at both cavitated and initial caries levels. RESULTS: The groups were balanced at baseline. After two years, 961 children (94.4%) were reexamined. The FV group showed a mean DMFS increment of 0.36 compared to 0.41 in the FMR group. The corresponding values for initial caries lesions were 0.83 and 0.91 respectively. CONCLUSION: There were no statistically significant differences in caries development over two years among children participating in a school-based fluoride varnish or mouth rinse program.

Effect of Probiotic Bacteria on Oral Candida in Frail Elderly.

The aim of this study was to investigate the effect of a daily intake of probiotic lactobacilli on the prevalence and counts of oral Candida in frail elderly patients living in nursing homes. The study had a double-blind randomized placebo-controlled design with 2 parallel arms. The study group consisted of 215 older adults (range, 60 to 102 y) who were enrolled after informed consent. After baseline examination and randomization, the subjects were given 1 lozenge containing 2 strains of the probiotic bacterium Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) or placebo twice daily (morning and evening). The intervention period was 12 wk, and saliva and plaque samples were collected at baseline and follow-up. The primary end point was prevalence of high Candida counts assessed from chairside tests. Secondary end points were levels of dental plaque and gingival inflammation. The groups were balanced at baseline. The attrition rate to follow-up was 19%. There was a statistically significant reduction in the prevalence of high Candida counts in the probiotic group but not in the placebo group, and the difference was statistically significant in both saliva and plaque (P < 0.05). No significant differences between the groups were noted concerning the levels of supragingival plaque or bleeding on probing. Thus, daily use of probiotic lozenges may reduce the prevalence of high oral Candida counts in frail elderly nursing homes residents (ClinicalTrials.gov NCT02391532).

Effect of tablets containing probiotic bacteria (Lactobacillus reuteri) on early caries lesions in adolescents: a pilot study.

The objective of the study was to investigate the effect of tablets containing probiotic lactobacilli on early caries lesions in adolescents with quantitative light-induced fluorescence (QLF). 36 healthy adolescents of both sexes (12-17 years of age) were enrolled and randomly allocated to a placebo-controlled trial with two parallel groups. The test group received two tablets daily containing two strains of Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) for a period of three months, while the control group got identical placebo tablets without live bacteria. The primary outcome was QLF-readings (change in fluorescence, ΔF and lesion area, mm2) at baseline and after 3 months, conducted at two buccal sites of each individual, pre-selected with clearly visible clinical signs of enamel demineralisation (white spots). Significantly more premolars were allocated to the placebo group, while the test group had more incisors (P<0.05). There were no statistically significant differences in fluorescence values between the groups, neither at baseline, nor at the follow-up. There was however a significant decrease in fluorescence over time in the test group, but not in the placebo group (P<0.05). No alterations of the lesion area (ΔA) were found in any group. The inter-examiner intra-class correlation coefficient-value for QLF-readings was excellent. No side- or adverse effects were reported during the intervention period. This pilot study found a significant decrease over time in the test group. However, no statistically significant differences in fluorescence values between the groups were found. Hence, the null hypothesis could not be rejected.

Lactobacillus reuteri influences regrowth of mutans streptococci after full-mouth disinfection: a double-blind, randomised controlled trial.

This study assessed whether the persistence of Lactobacillus reuteri DSM 17938 and ATCC PTA 5289 in saliva could delay the regrowth of mutans streptococci (MS) after a full-mouth disinfection with chlorhexidine (CHX). A randomised, double-blind, placebo-controlled study with a 6-week intervention period and 3- and 6-month follow-up was performed. 62 healthy subjects with moderate to high counts of MS were randomly assigned to a test group (n = 32) or a placebo group (n = 30). Before onset of the intervention, subjects received two sessions of professional cleaning, flossing, and application of CHX varnish and rinsed their mouth with a CHX solution between the sessions (2 days). Thereafter, the test group used probiotic lozenges (2/day) containing L. reuteri (DSM 17938 and ATCC PTA 5289; 1 × 10(8) CFU of each strain), and the placebo group used identical lozenges lacking the lactobacilli. Saliva samples were collected and cultured onto selective media, and isolates of L. reuteri as well as DNA directly extracted from saliva were tested by polymerase chain reaction (PCR) with specific primers. Presence of salivary MS was analysed with a chair-side test. L. reuteri was frequently detected by culture during the intervention period but in only 3 test group subjects at follow-ups. Regrowth of MS statistically significantly differed depending on the presence or absence of L. reuteri DSM 17938 detected by PCR. We conclude that cultivable L. reuteri strains may only sporadically be confirmed after termination of the intervention, but subjects with PCR-detected L. reuteri demonstrated slower regrowth of MS.

Probiotics for caries prevention and control.

Modulation of the microbiota for restoring and maintaining health is a growing issue in medical science. A search for relevant clinical trials on the use of probiotic bacteria as a potential and clinically applicable anti-caries measure was performed. According to predetermined criteria, papers were selected and key data on study design, sample size, intervention, duration, and results were extracted. Two animal and 19 human studies were retrieved. Most studies were short-term and restricted to microbiological endpoints, and only 3 human studies reported a caries endpoint. A high degree of heterogeneity among the included investigations hampered the analysis. Significant reductions of mutans streptococci in saliva or plaque following daily intake of probiotic lactobacilli or bifidobacteria were reported in 12 out of 19 papers, whereas 3 reported an increase of lactobacilli. Three caries trials in preschool children and the elderly demonstrated prevented fractions of between 21% and 75% following regular intakes of milk supplemented with L. rhamnosus. No adverse effects or potential risks were reported. The currently available literature does not exclude the possibility that probiotic bacteria can interfere with the oral biofilm, but any clinical recommendation would be premature. Large-scale clinical studies with orally derived specific anti-caries candidates are still lacking.

Probiotic supplements (Lactobacillus reuteri DSM 17938 and ATCC PTA 5289) do not affect regrowth of mutans streptococci after full-mouth disinfection with chlorhexidine: a randomized controlled multicenter trial.

The aim of this study was to investigate the effectiveness of tablets containing two probiotic Lactobacillus reuteri strains in inhibiting regrowth of salivary mutans streptococci (MS) after full-mouth disinfection (FMD) with chlorhexidine. The null hypothesis was that the levels of MS would not differ in comparison with a placebo protocol. The study population was comprised of 62 young adults (mean age 23 years) with moderate or high counts of salivary MS who volunteered after informed consent. The study was a double-blinded randomized controlled trial with two parallel groups. After a 3-day chlorhexidine regimen, the subjects were randomly assigned to a test group (n = 32) with probiotic lozenges (2/day) or a placebo group (n = 30). The intervention period was 6 weeks, and stimulated whole saliva was collected at baseline and after 1, 6, and 12 weeks. The samples were processed for MS by a chair-side test and DNA-DNA hybridization as an estimate of 19 bacterial strains associated with oral health and disease. There was no significant difference between the groups at inclusion, and FMD reduced the salivary MS levels significantly in both groups. The MS suppression lasted less than 6 weeks and there were no statistical differences in salivary MS regrowth between the test and control groups at any of the follow-ups. Likewise, there were no major differences in the regrowth patterns of the checkerboard panel between the two groups. We conclude that daily oral administration of L. reuteri did not seem to affect or delay the regrowth of salivary MS after FMD with chlorhexidine.

Transporting children with orthopaedic conditions and surgeries.

While motor vehicle crashes remain one of the leading causes of death and injury to children, proper and consistent use of child safety seats and safety belts can greatly improve children's chances of survival in motor vehicle crashes. Children with orthopaedic conditions and children after orthopaedic surgery, however, may be restricted to specialized child restraint options that are capable of providing proper fit and safe travel for a period of time after the procedure. To assure proper selection and avoid secondary injury, parents and health care professionals need to be aware of best practices for transporting children postoperatively and of restraint options that exist for children with orthopaedic conditions.

Development of the vertebrate small intestine and mechanisms of cell differentiation.

The intestinal epithelium represents an attractive biological model of differentiation from stem cells to highly differentiated epithelial cells, not only during particular developmental events depending upon the vertebrate species considered but also throughout adult life. The ontogenic maturation of the intestinal epithelium arises from both a programmed expression of specific genes and epigenetic influences mainly due to epithelial and mesenchymal interactions and hormonal participation. In the present paper we review the structural and functional changes that occur in the amphibian, avian and mammalian intestine during embryonic and/or post-embryonic development. Furthermore, we review the data concerning the mechanisms which control the cytodifferentiation of the intestinal epithelium.