The impact of small intestinal bacterial overgrowth on the growth of children and adolescents / Impacto do sobrecrescimento bacteriano no intestino delgado sobre o peso e a estatura de crianças e adolescentes

ABSTRACT Objective: To evaluate the association between small intestinal bacterial overgrowth (SIBO) and weight and height impairment in children and adolescents with gastroenterology diseases. Methods: Observational and retrospective study. All 162 patients aged less than 19 years old who underwent breath test in search of SIBO between 2011 and 2016 were studied. Breath test was collected after the intake of 10 grams of lactulose. The concentration of hydrogen and methane was measured for 180 minutes after the beginning of the test by 12i QuinTronMicroLyzer device. Results: SIBO was identified in 51 (31.5%) patients. There was no difference between the age of those with (mean=8.7y.o; 25th and 75th percentile: 4.6 and 11.3) and without (mean=7.9y.o 25th and 75th percentile: 4.8 and 12.2) SIBO (p=0.910). There was no association between gender and SIBO (male 26.3% vs. female 36.3%, p=1.00). A lower median of height-for-age Z score (mean=-1.32; 25th and 75th percentile: -2.12 and -0.08 vs. mean=-0.59; 25th and 75th percentile: -1.57 and 0.22; p=0.04) was demonstrated in children with SIBO when compared with children without it. There was no difference between the BMI-for-age Z score of patients with (mean=-0.48) and without SIBO (mean=-0.06) (p=0.106). The BMI of patients with SIBO (median=15.39) was lower than of those without it (median=16.06); however, the statistical analysis was not significant (p=0.052). The weight-for-age Z score was lower in patients with SIBO (mean=-0.96) than in those without SIBO (mean=-0.22) (p=0.02) Conclusions: Children and adolescents with SBIO associated with diseases of the gastrointestinal tract have lower weight and height values.

RESUMO Objetivo: Avaliar a existência de associação entre sobrecrescimento bacteriano no intestino delgado (SBID) e comprometimento de peso e estatura em crianças e adolescentes com doenças do aparelho digestivo. Métodos: Estudo observacional e retrospectivo em ambulatório de gastroenterologia pediátrica. Foram incluídos todos os 162 pacientes com idade inferior a 19 anos que realizaram teste respiratório para pesquisa de SBID entre 2011 e 2016. O teste respiratório foi realizado após ingestão de dez gramas de lactulose. Foram determinadas as concentrações de hidrogênio e metano em aparelho 12i QuinTron MicroLyzer até 180 minutos após o início do teste respiratório. Resultados: SBID foi caracterizado em 51 (31,5%) dos 162 pacientes. Não houve diferença na idade das crianças com (mediana=8,7 anos; percentil 25-75: 4,6-11,3) e sem (mediana=7,9 anos; percentil 25-75: 4,8-12,2) SBID (p=0,910). Não se observou associação entre SBID e sexo (masculino 27,4% e feminino 36,6%; p=0,283). O escore Z da estatura-idade nos pacientes com SBID (mediana=-1,32; percentil 25-75: -2,12—0,08) foi menor (p=0,040) do que naqueles sem SBID (mediana=-0,59; percentil 25-75: -1,57-0,22). Na comparação do escore Z de índice de massa corpórea-idade não foi observada diferença entre os grupos com (média=-0,489±1,528) e sem (média=-0,067±1,532) SBID (p=0,106). Nos pacientes com menos de 10 anos de idade, o escore Z de peso-idade foi menor nos pacientes com SBID (média=-0,968±1,359) do que nos sem SBID (média=-0,223±1,584) (p=0,026). Conclusões: Crianças e adolescentes com SBID associado a doenças do trato gastrintestinal apresentam menores valores de peso e estatura.

Minimal Hepatic Encephalopathy in Cirrhosis- How Long to Treat?

Abstract: Introduction. Minimal hepatic encephalopathy (MHE) can reverse after short-term treatment. However, relapse rate of MHE after stopping treatment has not been studied so far. We aimed to evaluate long-term (9 months) efficacy of a short-term (3 months) treatment of MHE with lactulose/rifaximin, for maintenance of remission from MHE. Material and methods. In this prospective study, consecutive patients with cirrhosis and MHE were treated with lactulose/rifaximin for 3 months. After treatment, they were followed up for 6 months. Psychometric testing for diagnosis of MHE was performed at baseline, 3 months and 9 months. Results. Of the 527 patients screened, 351 were found eligible and tested for MHE. Out of these, 112 (31.9%) patients had MHE (mean age 55.3 years; 75% males). They were randomized to receive Rifaximin (n = 57; 1,200 mg/day) or Lactulose (n = 55; 30-120 mL/day) for three months. At 3 months, 73.7% (42/57) patients in Rifaximin group experienced MHE reversal compared to 69.1% (38/55) in Lactulose group (p = 0.677). Six months after stopping treatment, 47.6% (20/42) in rifaximin group and 42.1% (16/38) patients in lactulose group experienced MHE relapse (p = 0.274). The overt hepatic encephalopathy development rate (7.1% vs. 7.9%) and mortality rate (0.23% vs. 0%) were similar in both groups. The Child-Turcotte-Pugh score and model for end stage liver disease (MELD) scores of patients who had MHE relapse were higher compared to those who didn’t. On multivariate regression analysis, MELD score was an independent predictor of MHE relapse. Conclusion. Of the patients who became MHE negative after short-term (3 months) treatment with rifaximin/lactulose, almost 50% had a relapse of MHE at 6 months follow-up.

Efeito da lactulose sobre os teores séricos de ureia, creatinina, cálcio e fósforo em cães não azotêmicos / Effect of lactulose on serum urea, creatinine, calcium and phosphorus in non-azothemic dogs

The present study evaluated serum levels of urea, creatinine, calcium and phosphorus in non-azothemic dogs by continued use of lactulose orally. Serum levels of urea, creatinine, calcium and phosphorus were determined in Beagle dogs, clinically healthy and without biochemical changes (non-azothemic), undergoing oral treatment with lactulose (n = 6), for a period of 30 days. The prebiotic showed no significant lowering effect on serum urea and creatinine, but the values of calcium and phosphorus, as well as their relation, were modified with reduced serum phosphorus levels in animals treated with lactulose compared to controls, with a significant difference...

El uso de inhibidores de bomba de protones y el hábito de fumar no modifican la tasa de sobrecrecimiento bacteriano intestinal en pacientes con patología digestiva funcional / Small intestinal bacterial overgrowth is not influenced by proton pump inhibitors and smoking habit in patient with funtional gastrointestinal disorders

Background: Drug induced inhibition of acid secretion has been associated to small intestinal bacterial overgrowth (SIBO). Smoking is followed by an increase of exhaled and orocecal transit time (OCTT). Aim: To investigate if the use of proton pump inhibitiors (PPI) and smoking can modifie the incidence of SIBO in patients with functional gastrointestinal disease. Patients and Methods: Questionnaires performed before a study for SIBO in patients with functional gastrointestinal disorders were analyzed. The use PPI and the smoking habit were recorded. The presence of SIBO and the OCTT was determined by means of the lactulose hydrogen breath test. Results: 437 patients, mean age 45 years (range: 14-93), 337 (77 percent) female, entered in the study SIBO was present in 356 patients, and 81 patients had normal H2 breath test. Both groups had a similar distribution of gender and age. The percentage of SIBO was no different in patients using PPI or presenting smoking habit Conclusions: Use of PPI and smoking habit are not risk factors for the development of SIBO in patients with functional disorders.

Los fármacos que inhiben la secreción gástrica favorecen el sobrecrecimiento bacteriano intestinal (SBI), mientras que el habito de fumar puede aumentar los niveles de H2 espirado y el tiempo de transito orocecal (TTOC). Objetivo: Investigar si el uso de inhibidores de la bomba de protones (IBP) y el habito de fumar modifican la incidencia de SBI en pacientes con trastornos digestivos funcionales. Pacientes y Métodos: Se analizaron encuestas de pacientes con patología digestiva funcional previas a un estudio de SBI Se consignaron el uso de IBP Y el hábito tabáquico en los 6 meses que precedieron al examen. La presencia de SBI y el tiempo de transito orocecal (TTOC) se determinaron con el test de hidrógeno en aire espirado con lactulosa. Resultados: 437 pacientes, con edad x 45 años (rango: 14-93),337 (77 por ciento) mujeres. Con SBI 356 pacientes, sin SBI 81 pacientes. Ambos grupos fueron comparables en cuanto a distribución por sexo y edad. El porcentaje de pacientes con SBI no fue diferente en pacientes con antecedente de uso de IBP o con hábito tabaquito. Conclusiones: El antecedente del uso de IBP y el tabaquismo no constituyen un factor de riesgo para SBI en pacientes con patología digestiva funcional.

Comparison of Rifaximin and Lactulose for the Treatment of Hepatic Encephalopathy: A Prospective Randomized Study

Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p=0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the post- treatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0-->> 4.2, p=0.000) ; lactulose group (11.3-->> 5.0, p=0.000) ). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy.

Sub chronic toxicity studies of lactulose in rats.

Lactulose has profound health benefits by way of increasing bifidobacterial flora in the intestine of infants thereby protecting them against enteric infection, constipation and systemic encephalopathy. In the present study to assess the sub chronic toxicity of lactulose syrup, the rats were fed on a basal feed supplemented with lactulose syrup at 0.5, 1.0, 2.0 and 5.0% for a period of 21 weeks. Monitoring of food consumption, gain in body weight and physical observations did not reveal any treatment-related toxicity in any of the group of rats. Terminal autopsy also did not reveal any signs of toxicity. Further, no significant alterations in relative organ weight, serum biochemistry and urinalysis were observed up to 1% lactulose supplementation level. The results suggest that supplementation of lactulose in the diet does not produce any toxicity at the doses tested.

Teste do H2 no ar expirado na avaliaçäo de absorçäo de lactose e sobrecrescimento bacteriano no intestino delgado de escolares / Breath hydrogen test to evaluate lactose absorption and small bowel bacterial overgrowth in children

Estudos realizados há mais de 10 anos demonstraram que a deficiência ontogenética de lactase é freqüente na população brasileira. Entretanto, esses estudos se basearam no incremento da glicemia após sobrecarga de doses não utilizadas habitualmente na dieta. Atualmente, aceita-se que a avaliação da absorção da lactose com o teste do hidrogênio no ar expirado é mais apropriada que o teste da curva glicêmica. Por outro lado, a enteropatia ambiental sintomática e/ou assintomática constituem um grave problema de saúde pública em grupos populacionais de baixo nível sócio econômico de nosso meio. A ocorrência de sobrecrescimento bacteriano no intestino delgado de crianças com enteropatia ambiental, foi caracterizada em crianças moradoras em favelas. Sobrecrescimento bacteriano no intestino delgado é caracterizado pela presença de bactérias pertencentes à flora colônica no intestino delgado. Objetivando avaliar a freqüência de má absorção de lactose e determinar a ocorrência de sobrecrescimento bacteriano no intestino delgado em crianças escolares, através do teste do H2 no ar expirado, investigaram-se 83 alunos de uma escola localizada na região periférica da cidade de Marília, Estado de São Paulo, após sobrecarga oral de lactose e lactulose. Foram colhidas também amostras de fezes para pesquisa de parasitas. Má absorção de lactose foi observada em 19 (22,9 por cento) escolares e intolerância à lactose em 10 (12,0 por cento). Sobrecrescimento bacteriano no intestino delgado foi identificado pelo teste do H2 no ar expirado em 6 (7,2 por cento) dos 83 escolares. Giardia lambia foi o parasita mais freqüentemente isolado nas fezes dos escolares. A ocorrência de deficiência ontogenética de lactase observada neste grupo de crianças foi semelhante ao relatado para populações caucasianas. Sobrecrescimento bacteriano foi encontrado neste grupo de crianças assintomáticas, podendo refletir as condições desfavoráveis de seu meio ambiente.

Assessment of protein quality of infant milk food formula supplemented with lactulose.

To examine the protein quality of infant food formula supplemented with lactulose (bifidogenic factor), groups of 21 day male weanling rats were fed diet containing lactulose at 0.5% for 4 weeks. The gain in body weight of rats fed lactulose supplemented diet were similar to that of rats fed lactulose free and skim milk powder fed diet as controls. No difference in overall acceptability pattern was also observed in studies conducted with human subjects for organoleptic evaluation. The results suggest that supplementation of lactulose in infant food formula does not affect either the protein quality as indicated by protein efficiency ratio in rats as compared to control formulae or overall acceptability by human subjects.

Gradiente transcraneana de citoquinas y permeabilidad intestinal en la injuria cerebral aguda severa / Transcranial cytokine gradient and intestinal permeability in severe brain injury

Background: Acute brain injury is associated with a bimodal hypermetabolic state probably caused by cytokine secretion and high hormone and catecholamine concentrations. In a first stage, the brain would produce these substances and afterwards, another production source, most probably the splanchnic territory, would perpetuate the hypermetabolic state. Aim: To investigate the cytokine production source and to assess intestinal permeability in acute brain injury in the absence of cerebral ischemia and systemic oxygen deficit. Patients and methods: Arterial systemic and cerebral venous bulbar interleukin 1 õ and interleukin 6 levels were measured during the first seven days of evolution in 15 patients with acute brain injury. Serum lactate, the oxygen/lactate ratio, gastric intramucosal pH and intestinal permeability using the lactulose/mannitol test were also assessed in the same period. Results: High arterial and venous interleukin 1 õ and interleukin 6 levels were detected. A positive gradient for interleukin 6 levels was detected throughout the study period with normal intramucosal pH, lactate and oxygen/lactate ratio. There was also an early impairment of intestinal permeability in these patients. Conclusions: High arterial and venous cytokine concentrations were detected in patients with acute brain injury. The positive gradient for interleukin 6 suggests a brain origin for this cytokine. Intestinal permeability is also altered in these patients

Asociación entre los niveles de amonio y GABA plasmáticos y el grado de encefalopatía hepática / Association of plasma ammonia and GABA levels and the degree of hepatic encephalopathy

Varias substancias presumiblemente tóxicas tales como el amonio se han implicado en la patogenia de la encefalopatía hepática porto-sistémica (EPS). Recientemente se ha propuesto la hipótesis del ácido gama-aminobutríco (GABA) donde el aumento del tono gabaérgico y la presencia de uno o más ligandos para el receptor GABA/benzodiacepínicos juegan un papel central. Con el objeto de investigar la asociación entre las elevaciones plasmáticas de amonio y GABA y el grado de encefalopatía hepática, estudiamos tres grupos de pacientes con enfermedad hepática que cursaban con episodio de EPS aguda espontánea o precipitada por hemorragia gastrointestinal o sepsis, en quienes se determinaron los niveles de amonio y GABA en plasma antes y después de tratamiento convencional con lactulosa. La EPS se valoró mediante el índice de EPs incluyendo pruebas del estado mental y electroencefalograma (EEG) entre otras. Los niveles de GABA en plasmas se encontraron significativamente elevados en pacientes con EPS pura (458+-108 pmol/mL) comparados con sujetos sanos (110+-23 pmol/mL)(p<0.01) aunque no se encontró correlación entre las concentraciones de GABA y el grado de encefalopátía. Sin embargo, los cambios en los niveles de amonio correlacionaron con los cambios en el índice de EPS (r=0.56;p<0.02) y con las alteraciones en el EEG (r=0.65;