Is the use of Lactobacillus reuteri probiotic efficient as adjunctive therapy in the treatment of periodontitis? A systematic review / O uso do probiótico Lactobacillus reuteri como terapia adjuvante no tratamento da periodontite é eficaz? Uma revisão sistemática

Objective: This systematic review had the purpose to validate the probiotic Lactobacillus reuteri as adjuvant therapy in the periodontal treatment of periodontitis, by the analysis of randomized controlled trial, controlled clinical trial, and observational studies. Material and Methods: Search keys related to the subject were defined, and the following databases were used as search strategies: MEDLINE via PubMed, Scopus, Web of Science, Cochrane Central Controlled Trials Registry, and EMBASE. The data selection and study were performed by two independent evaluators: first, they selected the article by title and abstract and subsequently qualified according to the bias risk analysis. A narrative synthesis has been performed based on the data obtained from the best-quality articles. After data extraction, their heterogeneity was analyzed, and a meta-analysis was performed. Results: In general, the results of the meta-analysis were positive for the use of probiotics as an adjuvant treatment. Considering the limitations of the comparisons between the analyzed articles studied, the conclusion was that probiotics may provide supplementary benefits to the treatment of periodontitis, with improvement in bleeding on probing rates and probing depth (AU)

Objetivo: Esta revisão sistemática teve como objetivo validar o uso do probiótico Lactobacillus reuteri como terapia adjuvante no tratamento periodontal da periodontite, por meio da análise de ensaios clínicos randomizados, ensaios clínicos controlados e estudos observacionais. Material e Métodos: Chaves de busca relacionadas ao assunto foram definidas, e as seguintes bases de dados foram utilizadas como estratégias de busca: MEDLINE via PubMed, Scopus, Web of Science, Cochrane Central Controlled Trials Registry e EMBASE. A seleção dos dados e o estudo foram realizados por dois avaliadores independentes: primeiro, selecionaram o artigo pelo título e resumo e posteriormente qualificaram de acordo com a análise de risco de viés. Uma síntese narrativa foi realizada com base nos dados obtidos dos artigos de melhor qualidade. Após a extração dos dados, sua heterogeneidade foi analisada e uma meta-análise foi realizada. Resultados: Em geral, os resultados da meta-análise foram positivos para o uso de probióticos como tratamento adjuvante. Considerando as limitações das comparações entre os artigos analisados estudados, concluiu-se que os probióticos podem trazer benefícios complementares ao tratamento da periodontite, com melhora nas taxas de sangramento à sondagem e na profundidade de sondagem (AU)

Intervención con probióticos para la prevención de enterocolitis necrotizante en prematuros extremos menores de 1500 gramos o de 32 semanas / Probiotic intervention to prevent necrotizing enterocolitis in extremely preterm infants born before 32 weeks of gestation or with a birth weight of less than 1500 g

Introducción. Existe evidencia del beneficio de los probióticos en prevenir enterocolitis necrotizante en prematuros extremos. Desde 2015, se usa probiótico preventivo en el Servicio de Neonatología, Hospital Hernán Henríquez Aravena, Temuco, Chile.Objetivo. Evaluar el impacto de este probiótico en la incidencia, gravedad, necesidad de terapia quirúrgica y letalidad por enterocolitis necrotizante en prematuros extremos. Pacientes y método. Estudio retrospectivo de cohortes. Datos analizados con Stata. Se aplicó la prueba exacta de Fisher para comparar porcentajes y, para los promedios, la prueba t para varianzas distintas. Los egresados entre 2015 y 2017 recibieron Lactobacillus reuteri Protectis (LRP), dosis única (1 x 108 unidades formadora de colonias) desde los primeros días de vida hasta cumplir las 36 semanas de edad gestacional corregida. Los controles egresados entre 2012 y 2014 no recibieron LRP.Resultados. El 3,45 % de los casos tuvo algún grado de enterocolitis: grado i (el 64 %), ii (el 18 %), iii (el 18 %); requirió cirugía el 18 % y no hubo letalidad. El 3,75 % de los controles históricos presentaron enterocolitis: grado i (el 12 %), ii (el 35 %), iii (el 53 %); el 64,7 % requirió cirugía, y el 47 % falleció. El grupo intervenido presentó grado ii o iii en un 36 %; en el grupo control, la sumatoria de estos estadios fue del 88 %.Conclusión.LRP administrado en dosis única diaria al prematuro extremo no modificó la incidencia de enterocolitis, pero disminuyó su gravedad, la letalidad y necesidad de tratamiento quirúrgico.

Introduction. There is evidence of the beneficial effects of probiotics to prevent necrotizing enterocolitis in extremely preterm infants. Probiotic prevention has been used since 2015 in the Division of Neonatology of Hospital Hernán Henríquez Aravena, Temuco, Chile.Objective. To assess the impact of this probiotic on the incidence, severity, surgical treatment requirement, and fatality rate of necrotizing enterocolitis in extremely preterm infants.Patients and methods. Retrospective, cohort study. Data were analyzed using Stata. Fisher's exact test was used to compare percentages, and the unequal variances t-test, for averages. Infants discharged between 2015 and 2017 received Lactobacillus reuteri Protectis (LRP), in a single dose (1 x 108 colony forming units), since the first days of life until 36 weeks of corrected gestational age. Controls discharged between 2012 and 2014 did not receive LRP.Results. Some degree of enterocolitis was observed in 3.45 % of cases: stage I (64 %), stage II (18 %), stage III (18 %); 18 % required surgery, and there were no deaths. Among historical controls, 3.75 % had enterocolitis: stage I (12 %), stage II (35 %), stage III (53 %); 64.7 % required surgery, and 47 % died. In the intervention group, stage II or III accounted for 36 % of cases, whereas in the control group, for 88 %.Conclusion. Administering a single daily dose of LRP to extremely preterm infants did not affect the incidence of enterocolitis, but reduced its severity, fatality rate, and surgical treatment requiremen

Risk and Protective Factors for Gastrointestinal Symptoms associated with Antibiotic Treatment in Children: A Population Study / 대한소아소화기영양학회지

6 years (RR=4.15), with previous abdominal pain (RR=7.2) or constipation (RR=4.06). Constipation was recorded in 23/289 (8.0%), with increased risk in children having surgery (RR=2.56) or previous constipation (RR=7.38). Probiotic supplementation significantly reduced AAD (RR=0.30) and abdominal pain (RR=0.36). Lactobacillus rhamnosus GG (LGG) and L. reuteri significantly reduced AAD (RR=0.37 and 0.35) and abdominal pain (RR=0.37 and 0.24).CONCLUSION: AAD occurred in 20.4% of children, with increased risk at younger age, lower respiratory and urinary tract infections, intravenous treatment and previous AAD. LGG and L. reuteri reduced both AAD and associated abdominal pain.

Sepsis por Lactobacillus reuteri en un recién nacido pretérmino: reporte de un caso / Sepsis due to Lactobacillus reuteri in an extreme preterm newborn: case report

La utilización de probióticos en la población neonatal ha contribuido a una disminución de la morbilidad y mortalidad en esta población a través de la reducción en la incidencia de entidades como enterocolitis necrosante, infecciones asociadas al cuidado de la salud y sepsis neonatal. A pesar de los múltiples efectos beneficiosos descritos, este tipo de medicamentos debe ser administrado con precaución en los pacientes de alto riesgo, debido a que se han documentado reportes de casos de sepsis neonatal por Lactobacillus rhamnosus, Saccharomyces boulardii y Bifidobacterium, entre otros. Se presenta un caso atípico de sepsis neonatal por Lactobacillus reuteri en un recién nacido pretérmino extremo en una institución de alta complejidad en la ciudad de Bogotá D. C., Colombia. El desenlace, en nuestro caso, fue fatal, pese al manejo médico establecido.

The use of probiotics in the neonatal population has contributed to a decrease in morbidity and mortality in this population through the reduction in the incidence of entities such as necrotizing enterocolitis, infections associated with health care and neonatal sepsis. Despite the multiple beneficial effects described due to the use of probiotics, this type of medication should be administered with caution in high-risk patients because reports of cases of neonatal sepsis by Lactobacillus rhamnosus, Saccharomyces boulardii and Bifidobacterium, among others, have been documented. We present an atypical case of neonatal sepsis due to Lactobacillus reuteri in an extreme preterm newborn in a highly complex institution in the city of Bogotá D. C., Colombia. The outcome in our case was fatal despite the established medical management.

Health Risk Assessment of a Food Supplement Containing Lactobacillus reuteri Protectis®

The Norwegian Scientific Commitee for Food Safety (VKM) appointed a working group of experts to answer a request from the Norwegian Food Safety Authority regarding health risk assessment of Lactobacillus reuteri Protectis® in a food supplement intended for use by infants and young children. The mandate of this health risk assessment was not to evaluate the health claims related to the products as such health claims are assessed by EFSA. The specific strain DSM 17938 is a “daughter strain” of the strain ATCC 55730 which was originally isolated from normal human milk. ATCC 55730 harbours two plasmids carrying transferable resistance genes against tetracycline and lincosamides respectively. The “daughter strain” DSM 17938 was established in 2008 by curing the ATCC 55730 for these plasmids, but is in all other respects claimed to be identical to ATCC 55730 and bioequivalence of the two strains has been suggested. The strain DSM 17938 was still resistant to tetracycline (although at a considerably lower level than ATCC 55730) and a number of other antibiotics, but these resistances were all considered being intrinsic by FBO. The absence of possible transferable/mobile genes has, to our knowledge, not been confirmed in later studies. We are not aware of any data indicating that L. reuteri has been the cause of serious human diseases – and none of the studies examined has reported any adverse or undesirable short time effects. It has also been used in preterm infants with dosage corresponding to the actual recommended doses - without reporting any adverse, short term reaction. There is therefore no evidence leading to consider the strain DSM 17938 at the dosage recommended as unsafe. However, more long-term data are still lacking and the long-term safety for the age groups considered in this assessment cannot be established. As evidence is accruing that the early microbial composition of the infant gut is important for the development of the gut flora and the immune system of the growing child, it is not possible to exclude that a daily supply of a particular bacterial strain over a prolonged period of time to an immature gastro-intestinal tract may have long-term, albeit still unknown, adverse effects on it’s development. As the long-term data are lacking it is not possible to answer whether the amount of the food supplement or the age of the infant or young child is of importance. However, if later long-term data should reveal any adverse reaction, it is reasonable to assume that the actual age group will be the most vulnerable. As the safety was not entirely established, the question of whether there are any vulnerable groups (i.e. premature, infants or children with diseases) where there are health risks associated with the intake of Lactobacillus reuteri Protectis®, as a food supplement was not considered.

Characterisation of the Probiotic Qualities Exhibited by Lactobacilli Strains Isolated from the Anogenital Tract

@#Introduction: Lactobacilli are well-documented probiotics that exert health benefits on their host. They exhibit characteristics that make them potential alternative treatments to address the antimicrobial resistance conundrum and diseases. Their mechanism of action varies with strain and species. Five lactobacilli strains previously isolated from the anogenital region were subjected to several assessments highlighted in the FAO/WHO document, ‘Guidelines for the Evaluation of Probiotics in Food’ to determine its suitability as potential probiotics. Methods: The five lactobacilli strains were subcultured onto Man de Rogosa agar (MRS). Their ability to auto- and co-aggregate was determined spectrophotometrically. Simultaneously, the cell surface hydrophobic properties of these strains towards xylene and toluene were evaluated using the microbial adhesion to hydrocarbon (MATH) test. The lactobacilli strains were also tested for their ability to withstand acid, bile and spermicide to determine their level of tolerance. Results: Lact. reuteri 29A, L. delbrueckii 45E and L. reuteri 29B exhibited the highest degree of auto- and co-aggregation properties. These lactobacilli strains also demonstrated high cell surface hydrophobicity, with the exception of L. delbrueckii 45E. Further tests to evaluate the isolated lactobacilli tolerance identified L. reuteri 29B as the most tolerant strain towards low pH (pH 2.5 for 4 h), high bile concentration (0.5% for 4 h) and high spermicides concentration (up to 10%). Conclusion: Out of the five lactobacilli strains which possessed high antimicrobial activities, L. reuteri 29B portrayed the best probiotic qualities with good auto- and co-aggregation abilities and high tolerance against acid, bile and spermicide

Lactobacillus reuteri DSM 17938 Improves Feeding Intolerance in Preterm Infants / 대한소아소화기영양학회지

PURPOSE: Feeding tolerance is extremely important in preterm infants. This study aimed to evaluate whether preterm infants receiving Lactobacillus reuteri DSM 17938 would develop fewer symptoms of feeding intolerance. Secondary outcomes were duration of parenteral nutrition, time to reach full feeding, length of hospital stay, sepsis, necrotizing enterocolitis (NEC), diarrhea, and mortality. METHODS: This double-blind randomized controlled trial of L. reuteri DSM 17938 versus placebo included 94 neonates with a gestational age of 28–34 weeks and birth weight of 1,000–1,800 g. RESULTS: Feeding intolerance (vomiting and/or distension) was less common in the probiotic group than in the placebo group (8.5% vs. 25.5%; relative risk, 0.33; 95% confidence interval, 0.12–0.96; p=0.03). No significant intergroup differences were found in proven sepsis, time to reach full feeding, length of hospital stay, or diarrhea. The prevalence of NEC (stages 2 and 3) was 6.4% in the placebo group vs. 0% in the probiotic group (relative risk, 1.07; 95% confidence interval, 0.99–1.15; p=0.24). Mortality rates were 2.1% in the probiotic group and 8.5% in the placebo group, p=0.36). CONCLUSION: The administration of L. reuteri DSM 17938 to preterm infants was safe and significantly reduced feeding intolerance. No significant differences were found in any other secondary outcomes.

The role of Lactobacillus reuteri DSM 17938 for the absorption of iron preparations in children with iron deficiency anemia / 소아과

PURPOSE: To determine whether Lactobacillus reuteri DSM 17938 plays a role in absorption of iron preparations given to children with iron deficiency anemia (IDA). METHODS: We performed a quasi-experimental study involving pre- and postintervention tests using a control group in North Sulawesi province, Indonesia, between July and September 2017. We conducted a single-blind controlled trial that included primary school children who were diagnosed with IDA based on reticulocyte hemoglobin equivalent (Ret-He) levels <27.8 pg/L. RESULTS: A total of 66 children were randomized into 2 groups. Thirty-four children received iron preparations with the addition of L. reuteri DSM 17938 (group 1), whereas the other 32 received iron preparations alone (group 2). The baseline Ret-He levels before intervention were similar in both groups. After 14 days of intervention, mean Ret-He level in group 1 changed from 24.43±1.64 to 28.21±1.72 pg/L (P=0.000). Mean Ret-He level in group 2 changed from 24.31±1.42 to 27.03±2.14 pg/L (P=0.000). Statistical analysis showed a significant increase in Ret-He levels in both groups; Ret-He levels were significantly higher in the experimental group than in the control group (P<0.05). CONCLUSION: Children with IDA receiving iron preparations with L. reuteri DSM 17938 for 14 days show higher Ret-He levels than those receiving iron preparations alone.

Effects of Lactobacillus reuteri on early feeding tolerance and infection prevention in preterm infants:A report of 93 cases / 中国实用儿科杂志

OBJECTIVE: To explore role of Lactobacillus reuteri DSM 17938 in the early feeding tolerance,growth and infection prevention of preterm infants. METHODS: The clinical data of 93 cases of preterm infants admitted between January 2017 and June 2018 to the First Department of Neonatology,Shengjing Hospital of China Medical University were analyzed retrospectively. All thecases weredividedintotheinterventiongroup(n=45)and the control group(n=48). Both groups of preterm infants were fed with the same type of premature infant formula and received parenteral nutrition if necessary. The intervention groupwas givena dose of 1×108 colony-forming units(5 drops)of Lactobacillus reuteri DSM 17938 once a day,until discharge.The control group did not take any probiotics. The early feeding tolerance,reflux,growth,nosocomial infection,neonatal necrotizing enterocolitis and adverse effects were observed in both groups of preterm infants. RESULTS: The incidence of vomiting,abdominal distension and gastric retention in the intervention group was lower than that in the control group(P0.05). The length of hospital stay was shorter in intervention group than in the control group(P<0.05). No adverse effects were found in the intervention group. CONCLUSION: Lactobacillus reuteri DSM 17938 can improve the early feeding tolerance of preterm infants,reduce reflux,promote growth and shorten the length ofhospitalstay.

Protective effect of against oxidative stress in neonatal mice with necrotizing enterocolitis / 南方医科大学学报

OBJECTIVE@#To investigate the protective effect of DSM17938 strain against oxidative stress in a neonatal mouse model of necrotizing enterocolitis (NEC) and explore the possible mechanism.@*METHODS@#Ninety-six 10-day-old neonatal C57BL/6J mice were equally randomized into control group, NEC group, and NEC+ group. The pathological changes of the ileocecal intestinal tissue were evaluated with HE staining and double-blind pathological scoring. The mRNA and protein expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the intestinal tissues were detected using quantitative real-time PCR and ELISA, respectively. Colorimetric assays were used to determine the activity of superoxide dismutase (SOD) and its inhibition rate, malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and GSSG/ GSH ratio.@*RESULTS@#Compared with those in the control group, the neonatal mice in NEC group showed significant weight loss ( 0.05).@*CONCLUSIONS@# DSM17938 can offer protection against NEC in mice by reducing oxidative stress and increasing antioxidant capacity of the intestinal tissue to suppress intestinal inflammations.

Efectos clínicos de Lactobacillus reuteri en el tratamiento de la gingivitis: Ensayo clínico aleatorizado controlado / Clinical effect of Lactobacillus reuteri in the treatment of gingivitis: a randomized controlled clinical trial

RESUMEN: Objetivo: Evaluar la eficacia de L. reuteri como adjunto en el tratamiento de la gingivitis. Material y Métodos: Se realizó un ensayo clínico aleatorizado placebo controlado en sujetos con gingivitis durante 3 meses. El grupo test recibió una tableta por día de la cepa probiótica Lactobacillus reuteri (dosis 2x10(8) UFC por día), el grupo control recibió las mismas tabletas pero sin bacterias vivas. La variable de resultado principal fue el índice gingival (IG), y las variables de resultado secundarias fueron el índice de placa (IP) y el índice de sangrado al sondaje (IS). Se realizó comparación intra e inter-grupos en el basal y al finalizar la intervención (3 meses). Resultados: Fueron incluidos en el análisis un total de 30 sujetos (15 test, 15 control). No hubo diferencias estadísticamente significativas entre los grupos en el basal (p> 0.05). Después de 3 meses de intervención se produjo en ambos grupos una disminución estadísticamente significativa en el índice gingival, índice de sangrado al sondaje e índice de placa (p< 0.05). Se detectó una significativa reducción en el número de sitios con IG 2 solo en el grupo test (p< 0.05). Conclusiones: El uso de tabletas de probiótico con L. reuteri como adjunto en el tratamiento de la gingivitis, produce una significativa reducción en el número de sitios que presentan inflamación más severa.

ABSTRACT: Aim: To evaluate the efficacy of L. reuteri as adjunct in the treatment of the gingivitis. Materials and Methods: A placebo-controlled clinical trial was conducted in gingivitis subjects for 3 months. Test treatment consisted of the administration of one tablet per day containing the probiotic strain Lactobacillus reuteri (doses 2x10(8) UFC per day), the control group received the same tablets but without live bacteria. The main outcome variable was the change in gingival index (GI), and the secondary outcome variables were the plaque index (PII) and the bleeding on probing (BoP). Outcome variables were compared between and within groups at baseline and at the end of intervention (3 months). Results: A total of 30 subjects (15 test, 15 control) were included in the analysis. No statistically significant differences were found between the groups at baseline (p> 0.05). Both treatment groups experienced a statistically significant improvement in the GI, PII and BoP (p < 0.05). There was a significant reduction in the number of sites with GI 2 only in the test group (p< 0.05). Conclusions: The use of probiotic tablets containing L. reuteri produces a significant reduction in the number of sites with severe inflammation.

Efeito da administração local ou sistêmica do Lactobacillus reuteri, no tratamento da doença periodontal experimentalmente induzida em ratos, submetidos à quimioterapia com 5-fluorouracil: estudo histopatológico, histométrico e imunoistoquímico / Effect of local or systemic administration of Lactobacillus reuteri in the treatment of experimentally induced periodontal disease in rats submitted to 5-fluorouracil chemotherapy: histopathological, histometric and immunohistochemical study

Introdução e objetivo: Os probióticos (PROs) estão sendo intensamente avaliados na prevenção ou tratamento de doenças da cavidade oral, que estão associadas a uma mudança na composição e atividade microbiana do biofilme e resposta do hospedeiro. O objetivo desse estudo foi avaliar o efeito do Lactobacillus reuteri aplicado localmente ou sistemicamente como coadjuvante ao tratamento periodontal não cirúrgico de raspagem e alisamento radicular (RAR), na periodontite experimentalmente induzida em animais submetidos ao tratamento com 5-fluorouracil (5-FU). Material e Métodos: A indução da periodontite experimental (PE) foi realizada com a colocação de um fio de algodão ao redor dos primeiros molares inferiores esquerdos de 108 ratos, que permaneceu por 7 dias. Todos os animais receberam o quimioterápico no momento da indução da PE (60mg/kg) e 48 horas após (40mg/kg) e foram separados aleatoriamente em 6 grupos com 18 animais cada um, com os seguintes tratamentos: 5FU: sem tratamento local ou sistêmico; 5FU/RAR: receberam tratamento com RAR seguido de 1 aplicação local de solução fisiológica salina (SS; 0,16mL); Grupo 5FU/SSL: RAR e 4 aplicações locais de SS (0,16mL); 5FU/SSS: RAR e 4 gavagens com SS (0,16mL); 5FU/PL: RAR e 4 aplicações locais de PRO (0,16 mL); 5FU/PS: RAR e 4 gavagens com PRO (0,16mL). 6 animais de cada grupo foram submetidos à eutanásia aos 7, 15 e 30 dias pós-tratamentos. A área da furca dos molares foi submetida às análises histopatológica, histométrica e dos padrões de imunomarcação para TRAP, PCNA, RANKL, OPG, OCN e TGF-ß1. Os dados obtidos foram submetidos à análise estatística (α=5%). Resultados: O grupo 5FU/PS apresentou melhora no processo inflamatório em todos os períodos. Houve maior perda óssea alveolar (PO) nos espécimes do grupo 5FU/SSS comparado ao 5FU/SSL (p˂0,01) no período de 7 dias de avaliação. No período de 15 dias os espécimes dos grupos 5FU/SSL e 5FU/SSS demonstraram maior PO comparado aos grupos 5FU (p˂0,05) e 5FU/PS (p˂0,05). Aos 30 dias a PO mostrou-se maior nos espécimes do grupo 5FU/PL comparado aos grupos 5FU/RAR (p˂0,05), 5FU/SSS (p˂0,05) e 5FU/PS (p˂0,05). Na análise intragrupo houve menor PO no grupo 5FU/RAR e 5FU/PS aos 30 dias em relação aos 7 dias (p˂0,05). Na imunomarcação de células TRAP-positivas não foi evidenciada diferença significante entre os grupos e períodos; houve maior imunomarcação de células PCNA-positivas aos 7 dias no grupo 5FU/RAR comparado ao 5FU/SSS. Prevaleceu baixo padrão de imunomarcação de TGF-ß1 e OCN nos grupos 5FU, 5FU/RAR, 5FU/SSL e 5FU/SSS e o grupo 5FU/PS apresentou aos 7 dias um moderado padrão de imunomarcação e aos 15 e 30 dias um alto padrão de imunomarcação. Na análise de RANKL prevaleceu um alto padrão de imunomarcação nos grupos 5FU, 5FU/RAR, 5FU/SSL, 5FU/SSS em todos os períodos e o grupo 5FU/PS apresentou aos 7 e 15 dias um moderado padrão de imunomarcação e aos 30 dias predominou um padrão de imunomarcação que variou do moderado ao baixo. Prevaleceu um padrão baixo de imunomarcação em todos os grupos experimentais e períodos, com exceção dos grupos 5FU/PL e 5FU/PS aos 30 dias (moderado padrão de imunomarcação) na análise de OPG. Conclusão: Diante dos resultados obtidos e com a metodologia empregada pode ser concluído que o uso sistêmico do Lactobacillus reuteri promoveu redução da inflamação e beneficiou o processo de reparação dos tecidos periodontais, porém não foi capaz de reduzir a PO na região de furca, demonstrando ser uma terapia periodontal coadjuvante promissora em animais submetidos à quimioterapia com 5-FU(AU)

Probiotics (PROs) have been intensively evaluated to prevent or treat oral cavity diseases, associated with a change in the composition and microbial activity of the biofilm and response of the host. The aim of this study was to evaluate the effect of Lactobacillus reuteri applied locally or systemically as a coadjuvant to the non-surgical periodontal treatment of scaling and root planing (SRP) in experimentally induced periodontitis in animals treated with 5-fluorouracil (5-FU). Induction of experimental periodontitis (EP) was performed by placing a cotton thread around the left lower molars of 108 rats, which were kept there for 7 days. All animals underwent chemotherapy twice. They were 60mg/kg at the time they were subjected to ligature induction and again another 40 mg/kg, 48 hours later. They were randomly divided into 6 groups with 18 animals each and they received the following treatments: 5FU: treated animals with 5-FU; 5FU/SRP: 5-FU treated animals receiving SRP treatment followed by physiological saline (SS) solution; 5FU/SSL group: animals treated with 5-FU, who received SRP treatment and local SS applications; 5FU/SSS: animals treated with 5-FU, who received SRP treatment and systemic treatment with SS; 5FU/PL: animals treated with 5-FU, who received SRP treatment and local applications of PRO; 5FU/PS: animals treated with 5-FU, who received SRP treatment and systemic treatment with PRO (0.16ml x 4 days). Six animals from each group were submitted to euthanasia at 7, 15 and 30 days after treatments. The area of the molar furcation was submitted to histopathological, histometric and immunolabeling analysis for TRAP, PCNA, RANKL, OPG, OCN and TGF-ß1. The data were submitted to statistical analysis (α = 5%). There was greater bone loss (BL) in the 5FU/SSS group compared to the 5FU/SSL group (p˂0.01) in the 7-day evaluation period. In the 15-day period, specimens from the 5FU/SSL and 5FU/SSS groups showed a higher BL compared to the 5FU (p˂0.05) and 5FU/PS (p˂0.05) groups. At 30 days the BL was higher in the 5FU/PL group compared to the 5FU/SRP (p˂0.05), 5FU/SSS (p˂0.05) and 5FU/PS groups (p˂0.05). In the intragroup analysis there was a lower BL in the 5FU/SRP group and 5FU/PS at 30 days compared to 7 days (p˂0.05).In the immunostaining of TRAP-positive cells no significant difference between groups and periods was evidenced; there was greater immunolabeling of PCNA-positive cells at 7 days in the 5FU/SRP group compared to 5FU/SSS. Low prevalence of TGF-ß1 and OCN immunostaining in the 5FU, 5FU/RAR, 5FU/SSL and 5FU/SSS groups prevailed at all periods. The 5FU/PS group presented at 7 days a moderate pattern of immunostaining and at 15 and 30 days a high standard of immunoblotting of TGF-ß1 and OCN; the 5FU/PL group presented a moderate pattern of TGF-ß1 and OCN immunoregulation at 7, 15 and 30 days; for RANKL a high standard of immunostaining in the 5FU, 5FU/SRP, 5FU/SSL, 5FU/SSS groups prevailed at all periods, 5FU/PL prevailed at 7 days a high standard of immunostaining and a moderate immunostaining pattern at 15 and 30 days and 5FU/PS showed a moderate immunostaining pattern at 7 and 15 days, and at 30 days a predominance of the immunoblot pattern varied from moderate to low; for OPG a low pattern of immunoblotting prevailed in all experimental groups and periods, except for 5FU/PL and 5FU/PS at 30 days that presented a moderate pattern of immunostaining. Based on the results obtained in this study and the methodology used to work on it, it was concluded that the use of Lactobacillus reuteri promoted reduction of inflamation and benefited the process of repairing periodontal tissues, but it was not able to reduce the BL in the furca region, proving to be a therapy promising adjuvant periodontal in animals submitted to 5-FU chemotherapy(AU)

Evaluation of the ability to metabolize 1, 2-propanediol by heterofermentative bacteria of the genus Lactobacillus

Background: New directions of research on lactic acid bacteria include investigation of metabolic pathways for the synthesis and/or metabolism of 1,2-propanediol, commonly used in the food and chemical industry, medicine, pharmacy and cosmetology as well as agriculture. The objective of this study was to compare the capacity of strains representing three diverse heterofermentative species belonging to the genus Lactobacillus to synthesize and/or transform 1,2-PD as well as to suggest new directions of research aimed at commercial use of this metabolite. Results: The novel strain of Lactobacillus buchneri A KKP 2047p, characterized as exhibiting an unusual trait for that species in the form of capacity to metabolize 1,2-PD, grew poorly in a medium containing 1,2-PD as a sole carbon source. The supplementation with glucose facilitated rapid growth of bacteria and use of 1,2-PD for the synthesis of propionic acid. A similar observation was noted for Lactobacillus reuteri. On the other hand, Lactobacillus diolivorans effectively metabolized 1,2-PD which was the sole carbon source in the medium, and the addition of glucose inhibited the synthesis of propionic acid. The experiments also investigated the effect of cobalamin as a diol dehydratase coenzyme involved in the propionic acid synthesis from 1,2-PD whose addition promoted the yield of the reaction in the case of all tested strains. Conclusions: All tested isolates showed the ability to effectively metabolize 1,2-PD (in the presence of cobalamin) and its conversion to propionic acid, which reveals that investigated bacteria meet the essential requirements of microorganisms with a potential application.

Cell surface proteins play an important role in probiotic activities of Lactobacillus reuteri

BACKGROUND: Eight Lactobacillus reuteri strains, previously isolated from breast-fed human infant feces, were selected to assess the potential contribution of their surface proteins in probiotic activity. These strains were treated with 5 M LiCl to remove their surface proteins, and their tolerance to simulated stomach-duodenum passage, cell surface characteristics, auto aggregation, adhesion, and inhibition of pathogen adhesion to Caco-2 cells were compared with untreated strains. RESULTS: The survival rates, auto aggregation, and adhesion abilities of the LiCl-treated L. Reuteri strains decreased significantly (p< 0.05) compared to that of the untreated cells. The inhibition ability of selected L. reuteri strains, untreated or LiCl treated, against adherence of Escherichia coli 25922 and Salmonella typh iNCDC113 to Caco-2 was evaluated in vitro with L. reuteri ATCC55730 strain as a positive control. Among the selected eight strains of L.reuteri, LR6 showed maximum inhibition against the E. Coli ATCC25922 and S. typhiNCDC113. After treatment with 5 M LiCl to remove surface protein, the inhibition activities of the lactobacilli against pathogens decreased significantly (p< 0.05). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated thatLR6 strains had several bands with molecular weight ranging from 10 to 100 KDa, and their characterization and functions need to be confirmed. CONCLUSIONS: The results revealed that the cell surface proteins of L. reuteri play an important role in their survivability, adhesion, and competitive exclusion of pathogen to epithelial cells.

Assessment of probiotic potential of Lactobacillus reuteri MD5-2 isolated from ceca of Muscovy ducks

Lactic acid bacteria (LAB) are commonly used as probiotics in poultry. The present study employed in vitro and in vivo methods to select and test LAB isolated from Muscovy duck ceca as potential probiotics. In the in vitro study, 50 LAB were isolated from Muscovy duck ceca and tested for growth inhibition against Salmonella (S.) Enteritidis. Eleven isolates strongly inhibited S. Enteritidis and only 1 isolate (MD5-2) showing the strongest inhibition was selected for identification. This isolate was called as Lactobacillus (L.) reuteri MD5-2. For the in vivo investigation, 90 1-day-old Muscovy ducks were randomly assigned into three groups of 30 animals each (group 1, control; group 2, treated with 108 colony-forming unit (CFU) of L. reuteri MD5-2 orally once on day 1; and group 3, treated with 108 CFU of L. reuteri MD5-2 orally once daily from days 1 to 5). The ducks were housed in three large cages and raised for 50 days, after which body weight, duodenal villus height and crypt depth were measured. Both villus height and villus height to crypt depth ratio were significantly greater in group 3 than in groups 1 and 2. In conclusion, further investigation of L. reuteri MD5-2 as a potential probiotic strain is warranted.

Lactobacillus reuteri DSM 17938 shortens acute infectious diarrhea in a pediatric outpatient setting / O Lactobacillus reuteri DSM 17938 reduz a diarreia infecciosa aguda no cuidado pediátrico ambulatorial

OBJECTIVE: Two randomized controlled clinical trials have shown thatLactobacillus (L) reuteri DSM 17938 reduces the duration of diarrhea in children hospitalized due to acute infectious diarrhea. This was the first trial evaluating the efficacy of L. reuteri DSM 17938 in outpatient children with acute infectious diarrhea.METHODS: This was a multicenter, randomized, single-blinded, case control clinical trial in children with acute watery diarrhea. A total of 64 children who presented at outpatient clinics were enrolled. The probiotic group received 1 × 108 CFU L. reuteri DSM 17938 for five days in addition to oral rehydration solution (ORS) and the second group was treated with ORS only. The primary endpoint was the duration of diarrhea (in hours). The secondary endpoint was the number of children with diarrhea at each day of the five days of intervention. Adverse events were also recorded.RESULTS: The mean duration of diarrhea was significantly reduced in the L. reuteri group compared to the control group (approximately 15 h, 60.4 ± 24.5 h [95% CI: 51.0-69.7 h] vs. 74.3 ± 15.3 h [95% CI: 68.7-79.9 h], p < 0.05). The percentage of children with diarrhea was lower in the L. reuteri group (13/29; 44.8%) after 48 h than the control group (27/31; 87%; RR: 0.51; 95% CI: 0.34-0.79,p < 0.01). From the 72nd hour of intervention onwards, there was no difference between the two groups in the percentage of children with diarrhea. No adverse effects related to L. reuteri were noted.CONCLUSION:L. reuteri DSM 17938 is effective, safe, and well-tolerated in outpatient children with acute infectious diarrhea.

OBJETIVO: Dois ensaios clínicos randomizados controlados demonstraram que oLactobacillus (L) reuteri DSM 17938 reduz a duração de diarreia em crianças hospitalizadas devido a diarreia infecciosa aguda. Este é o primeiro ensaio que avalia a eficácia do L. reuteri DSM 17938 em crianças com diarreia infecciosa aguda no ambulatório.MÉTODOS: Ensaio clínico multicêntrico, randomizado, único cego, com grupos paralelos e controlado em crianças com diarreia aguda. Foram inscritas 64 crianças internadas na clínica ambulatorial. O grupo probiótico recebeu 1 × 108 CFU L. reuteri DSM 17938 por cinco dias, além de uma solução de reidratação oral (SRO), e o segundo grupo foi tratado apenas com SRO. O desfecho principal foi a duração da diarreia (em horas). O desfecho secundário foi o número de crianças com diarreia em cada um dos cinco dias da intervenção. Os eventos adversos também foram registrados.RESULTADOS: A duração média da diarreia foi significativamente reduzida no grupoL. reuteri em comparação com o grupo de controle (aproximadamente 15 horas; 60,4 ± 24,5 horas [51,0-69,7 horas, IC de 95%] em comparação com 74,3 ± 15,3 horas [68,7-79,9 horas, IC de 95%], p < 0,05). O percentual de crianças com diarreia foi menor no grupo L. reuteri (13/29; 44,8%) após 48 horas do que no grupo de controle (27/31; 87%) (RR: 0,51; 0,34-0,79; IC de 95%, < 0,01). A partir da 72a hora de intervenção, não havia diferença entre os dois grupos no percentual de crianças com diarreia. Nenhum efeito adverso com relação ao L. reuteri foi observado.CONCLUSÃO: O L. reuteri DSM 17938 é eficaz, seguro e bem tolerado por crianças com diarreia infecciosa aguda no ambulatório.

Selection and immunomodulatory evaluation of lactic acid bacteria suitable for use as canine probiotics / 대한수의학회지

This study was conducted to isolate lactic acid bacteria (LAB) from dog intestine and identify potential probiotic strains for canine use. One hundred and one LAB were isolated from feces of 20 healthy dogs. Acid, bile, and heat resistance along with adherence to Caco-2 cells and antimicrobial activity against pathogens were examined. To analyze immunomodulative effects, the production of nitric oxide (NO), TNF-alpha, and IL-1beta was measured using RAW 264.7 macrophages. Additionally, RAW BLUE cells were used to evaluate nuclear factor-kappaB (NF-kappaB) generation. Ultimately, three strains were selected as canine probiotics and identified as Lactobacillus reuteri L10, Enterococcus faecium S33, and Bifidobacterium longum B3 by 16S rRNA sequence analysis. The L10 and S33 strains showed tolerance to pH 2.5 for 2 h, 1.0% Oxgall for 2 h, and 60degrees C for 5 min. These strains also had strong antimicrobial activity against Escherichia coli KCTC 1682, Salmonella Enteritidis KCCM 12021, Staphylococcus aureus KCTC 1621, and Listeria monocytogenes KCTC 3569. All three strains exerted better immunomodulatory effects than Lactobacillus rhamnosus GG (LGG), a well-known commercial immunomodulatory strain, based on NO, NF-kappaB, IL-1beta, and TNF-alpha production. These results suggested that the three selected strains could serve as canine probiotics.

Las posibilidades del empleo de lactobacilos en la gastroenterología y la nutrición humana / Therapeutic potential of the use of lactobacilli in gastroenterology and human nutrition

Lactobacilli are normal inhabitants of the human intestine. They are also present in maternal milk, where Lactobacillus reuteri was first described. This confirms that maternal milk transfers components of the maternal microbiota to the offspring. L. reuteri ATCC 55730 decreases the intensity and duration of infantile colic defined as episodes of strident crying for at least 3 hours, 3 times a week during 3 months. Its etiology is unknown but recent evidence shows that affected infants harbor less Iactobacilli and more Bacteroides in their feces. In 2008 it was shown that this strain carries plasmidia that could transfer resistance to antibiotics. For this reason L. reuteri it was cured of these factors and this resulted in L. reuteri DSM 17938 which is devoid of them; tests in vitro, in laboratory animals and in humans demonstrated that both strains are equivalent. The effect of L. reuteri in infantile colic may be explained by its blocking at the level of the dorsal ganglia of the spinal chord of the transmission to the central nervous system of afferent pain stimuli. L. reuteri has effects on gastroesophageal reflux probably through the acceleration of gastric emptying and it decreases the incidence and severity of necrotizing enterocolitis. Other positive effects are related to chronic constipation and acute diarrhea. L. reuteri synthesizes a molecule with intense bactericidal activity, β-hidroxy propenal o reuterin from glycerol, which may explain some of its effects. Lactobacillus rhamnosus GG ATCC 53103 is probably the probiotic that has been studied the most and for a longer period. It shortens the duration and it decreases the number of evacuations in acute diarrhea as well as the duration and frequency of vomiting. It also induces improvements of antibiotic associated diarrhea and of upper respiratory infections. The positive effects of Lactobacillus GG may be due to the stimulation of innate and adaptive immunity and to the activation of macrophages and of NK lymphocytes. One of its effects refers the response its administration induces in infants with atopy/eccema. Some studies have demonstrated that the severity and extent of the lesions is decreased after Lactobacillus GG administration, that may persist for some years after its administration has been ended. Lactobacillus GG also exerts positive effects on conditions such as the irritable bowel syndrome through mechanisms that are not known with certainty.

Los lactobacilos son habitantes normales de las mucosas de los seres humanos; también están presentes en la leche materna. Lactobacillus reuteri fue descrito en la leche de una madre peruana, lo que confirma que estas bacterias son parte de la microbiota que las madres transfieren a sus hijos. El cólico infantil son episodios de llanto excesivo, estridente, por a lo menos 3 horas 3 veces por semana y por a lo menos 3 meses. L. reuteri ATCC 55730 demostró disminuir su intensidad y duración. La etiología del cólico se desconoce pero en las heces de los lactantes afectados se han demostrado disminuciones de los lactobacilos y aumentos de Bacteroides. En 2008 se demostró que L. reuteri ATCC 55730 era portador de plasmidios capaces de resistencia a antibióticos por lo que fue "curado" de estos factores y resultó una nueva cepa, denominada DSM 17938; pruebas in vitro y en animales mostraron su inocuidad y ensayos en humanos revelaron que ejerce las mismas propiedades benéficas que la cepa original. El efecto de L. reuteri en el cólico infantil puede estar relacionado con su capacidad de bloquear en los ganglios dorsales de la medula espinal la transmisión de estímulos a los centros cerebrales superiores. El efecto antirreflujo de L. reuteri se debería a la aceleración del vaciamiento gástrico. Ambas cepas de esta bacteria disminuyen la progresión, morbilidad y mortalidad de la enterocolitis necrosante. Otros efectos en la constipación crónica y la duración de la diarrea aguda de distintas etiologías. L. reuteri sintetiza una molécula, el β-hidroxipropenal o reuterina, con actividad antibacteriana. Lactobacillus rhamnosus GG ATCC 53103 es probablemente el probiótico más estudiado; acorta la duración de la diarrea aguda, disminuye el número de evacuaciones y la duración de los vómitos e induce mejorías de la diarrea asociada con los tratamientos antibióticos; y disminuiría la intensidad de las infecciones respiratorias altas. Sus efectos se deberían a la estimulación de las inmunidades innata y adquirida y de la activación de los macrófagos y los linfocitos NK. Un efecto notable y discutido de L. ramnosus GG se refiere a sus efectos en la atopia cutánea, ya que disminuiría la extensión e intensidad de sus síntomas, incluso más allá de su administración. También ejercería efectos sobre cuadros funcionales gastrointestinales como el síndrome del intestino irritable, por mecanismos aun no elucidados.

Probiotics association in the suckling and nursery in piglets challenged with Salmonella typhimurium

This work aimed to study the probiotics association in 144 piglets from birth to 62 days old. In lactation, the design was completely randomized with two treatments, CTL, 1 mL of distilled water and ProbA, 5g in 15 ml of distilled water, both orally, and in the nursery in randomized block design, with 2x3 factorial arrangement of treatments, ProbA ProbB: 30g/ton of ProbB in the ration; CTL ProbB: 30g/ton of ProbB in the ration; ProbA ProbA, CTL CTL; ProbA CHA (challenged); CTL CHA. At 35 days of age the animal of the nursery were inoculated with Salmonella typhimurium orally. There was no effect of the parameters evaluated during the maternity. In nursery, the feed conversion was favorable to the ProbA. In the evaluation of fecal score, the challenged group had more diarrhea and increased elimination of S. typhimurium. Results showed the positive action of probiotics when applied at birth by the direct influence on the formation of the intestinal microbiota.

Molecular characterisation and biomass and metabolite production of Lactobacillus reuteri LPB P01-001: a potential probiotic

Lactobacillus reuteri LPB P01-001 was isolated from the gastrointestinal tract of wild swine and was characterised by biochemical testing and sequencing of gene 16S rRNA. A simple and low-cost culture medium based on cane sugar (2.5% p/v) and yeast extract (1% p/v) was used in the production of this probiotic. The fermentative conditions were a) pH control at 6.5 and b) no pH control; both were set at 37°C in a 12 L slightly stirred tank bioreactor. Fermentation parameters such as the specific growth rate, productivity and yield of biomass, lactic and acetic acid levels were determined. L. reuteri LPB P01-001 behaves as an aciduric bacteria because it grows better in a low pH medium without pH control. However, the lactic acid production yield was practically half (9.22 g.L-1) of that obtained under a constant pH of 6.5, which reached 30.5 g.L-1 after 28 hours of fermentation. The acetic acid production was also higher under pH-controlled fermentation, reaching 10.09 g.L-1 after 28 hours of fermentation. These parameters may raise the interest of those committed to the efficient production of a probiotic agent for swine.