Investigations on the bacterial flora, pH, and sugar content in the intestinal tract of infants

Barbero, Giulio J.; Runge, Gretchen; Fischer, Doane; Crawford, Mary N.; Torres, Francisco Eduardo; György, Paul

doi:10.1016/s0022-3476(52)80176-3

Cited by 67 publications

(29 citation statements)

References 13 publications

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“…No stool pH measurements were reported, but these conditions generally produce acidic fecal contents (12,25 5.0, a specific pH above which a rise in H2 excretion occurs in response to malabsorbed carbohydrate cannot be established with certainty from these data. Moreover, attempts to identify a minimum stool pH above which H2 breath tests can be interpreted by current criteria must also take into account that fecal pH may not accurately reflect the pH more proximally in the colon (15).…”

Section: Discussionmentioning

confidence: 94%

“…Gas production in vitro from bean homogenates by canine intestinal bacteria is inhibited at acidic pH (8), and Vince et al (9) have recently demonstrated that generation of ammonia by colonic bacteria is pH dependent. Colonic pH is frequently acidic in individuals on certain modified diets (11) and in normal newborns (12). Luminal bacterial metabolism of dietary carbohydrates may be altered and H2 production reduced in these subjects, which may affect the interpretation of H2 breath tests used in the diagnosis of carbohydrate malabsorptive states.…”

Section: Introductionmentioning

confidence: 99%

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Role of pH in production of hydrogen from carbohydrates by colonic bacterial flora. Studies in vivo and in vitro.

Perman¹,

Modler²,

Olson³

1981

J. Clin. Invest.

191

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A B S T R A C T Hydrogen produced by colonic bacteria and excreted in breath is a useful index ofcarbohydrate malabsorption. Since colonic contents are often acidic in individuals with carbohydrate malabsorption and in normal newborns, we determined the effect of colonic acidification on H2 production. Acidification of colonic contents by dietary means significantly reduced excess breath H2 excretion from 55.4+ 11.1 (SEM) to 12.2 ±3.1 ml/4 h (P < 0.05) after administration of 0.3 g/kg of the nonabsorbable sugar lactulose to five normal adult subjects. Similarly, the breath H2 response to lactose was reduced or eliminated in two proven lactose malabsorbers after acidification. The correlation between pH and H2 production from carbohydrate was further investigated in adults and neonates, using an in vitro fecal incubation system. Glucose disappearance and H2 production were pH dependent and highly correlated (r = 0.94) in the pH range 5.5-7.6. Maximal production of H2 from glucose by fecal incubates occurred at pH 7.0-7.45. Inhibition of H2 production from carbohydrate occurred at acid pH. H2 per hour from glucose at pH 6.2 and 5.5 averaged 60.2% and 24.2%, respectively, of that produced at neutral pH. Rapid reversal of pH-induced inhibition by neutralization indicated a metabolic, rather than a bactericidal process. The observations indicate that the breath H2 response to malabsorbed carbohydrate is affected by colonic pH. It appears that the efficiency of bacterial carbohydrate metabolism in the colon is pH dependent.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Role of pH in production of hydrogen from carbohydrates by colonic bacterial flora. Studies in vivo and in vitro.

Perman¹,

Modler²,

Olson³

1981

J. Clin. Invest.

191

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“…Another study reported the similar duodenal pH between children aged 0.5-12 years and adults (15). Limited information pertaining to the luminal pH of small intestine was reported for neonates by Barbero et al (16), through our comprehensive literature searches in MEDLINE and EMBASE databases (from inception to June, 2014). In the study by Barbero et al (16), the enteric fluids in various segments of small intestine were obtained from normal neonates and young infants (2 weeks to 3 months of postnatal age) by intestinal intubation combined with aspiration technique.…”

mentioning

confidence: 89%

“…Limited information pertaining to the luminal pH of small intestine was reported for neonates by Barbero et al (16), through our comprehensive literature searches in MEDLINE and EMBASE databases (from inception to June, 2014). In the study by Barbero et al (16), the enteric fluids in various segments of small intestine were obtained from normal neonates and young infants (2 weeks to 3 months of postnatal age) by intestinal intubation combined with aspiration technique. Individual pH values reported by Barbero et al (16) were captured via computer digitization, and subsequently summarized by descriptive statistics.…”

mentioning

confidence: 99%

“…In the study by Barbero et al (16), the enteric fluids in various segments of small intestine were obtained from normal neonates and young infants (2 weeks to 3 months of postnatal age) by intestinal intubation combined with aspiration technique. Individual pH values reported by Barbero et al (16) were captured via computer digitization, and subsequently summarized by descriptive statistics. Duodenal, jejunal, and ileal pH in seven neonates and infants who were exclusively breast-fed were 6.4±0.5, 6.6±0.4, and 6.9±0.7, respectively; while duodenal, jejunal, and ileal pH in eight neonates and infants who were fed solely with cow's milk were 6.3±0.9, 6.0±0.5, and 6.3±0.8, respectively.…”

mentioning

confidence: 99%

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Similarities and Differences in Gastrointestinal Physiology Between Neonates and Adults: a Physiologically Based Pharmacokinetic Modeling Perspective

Zheng

2014

AAPS J

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Abstract. Physiologically based pharmacokinetic (PBPK) modeling holds great promise for anticipating the quantitative changes of pharmacokinetics in pediatric populations relative to adults, which has served as a useful tool in regulatory reviews. Although the availability of specialized software for PBPK modeling has facilitated the widespread applications of this approach in regulatory submissions, challenges in the implementation and interpretation of pediatric PBPK models remain great, for which controversies and knowledge gaps remain regarding neonatal development of the gastrointestinal tract. The commentary highlights the similarities and differences in the gastrointestinal pH and transit time between neonates and adults from a PBPK modeling prospective. Understanding the similarities and differences in these physiological parameters governing oral absorption would promote good practice in the use of pediatric PBPK modeling to assess oral exposure and pharmacokinetics in neonates.KEY WORDS: gastric emptying; gastrointestinal pH; neonates; physiologically based pharmacokinetic modeling; small intestinal transit time.Although physiologically based pharmacokinetic (PBPK) modeling holds great promise for facilitating pediatric drug development and regulatory review, the implementation and interpretation of pediatric PBPK models continues to face challenges, in which controversies and knowledge gaps remain regarding neonatal development of the gastrointestinal tract. In this context, we would like to offer some comments on the recent article of Khalil and Läer (1). In the work by Khalil and Läer (1), inaccurate predictions of oral pharmacokinetics of sotalol, using two PBPK models, were observed in neonates. The authors ascribed the poor predictions to factors related to the absorption rather than elimination or distribution processes and highlighted the lack of many age-specific physiological alterations in the parameterization of the used pediatric absorption models. Apart from the ontogeny of intestinal transporters and drugmetabolizing enzymes, the authors argued that gastrointestinal pH profiles and transit time should be considered as agerelated physiological variables to improve the predictive power of pediatric PBPK models. In this commentary, we provide additional information to facilitate a better understanding of the similarities and differences in gastrointestinal physiology between neonates and adults, which are of critical importance when using PBPK models to simulate oral pharmacokinetics in neonates.Despite the neutral pH in newborn stomach at delivery has been well recognized (2,3), much of the literature is replete with contradictory information on the maturation of gastric pH during the neonatal period. Some suggested that the neonatal gastric pH is greater than 5, which is quite different from the adult level (4-6); but others believed that the gastric pH of neonates stays within a more acidic range of 2-3, which is similar to that of adults (7,8). Upon careful examination of the reported n...

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Role of Feeding and Vitamin K in Hypoprothrombinemia of the Newborn

Keenan¹,

Jewett²,

Glueck³

1971

Arch Pediatr Adolesc Med

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Whole blood prothrombin times were determined serially in five groups of randomly selected well newborn "term" infants, none of whom had clinical evidence of bleeding. Prothrombin values in infants given menadione sodium bisulfite (vitamin K) parenterally shortly after birth were stable. The remainder of the infants who were not given vitamin K were divided into subgroups. Twenty-four hours after the first feeding, prothrombin activity of infants fed cow's milk did not differ significantly from that of infants given vitamin K at birth. In contrast, prothrombin times 24 hours after the first feeding of breast fed infants, of infants given bottled human milk, or of infants receiving only sterile water, were all significantly longer than that of infants given vitamin K parenterally. The responses of these newly born infants to the various feeding regimens appear to represent an in vivo assay for dietary vitamin K. The data document hypoprothrombinemia in the majority of infants who do not receive vitamin K parenterally and emphasize the importance of the administration of a small prophylactic dose of the vitamin to all newly born infants.

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Investigations on the bacterial flora, pH, and sugar content in the intestinal tract of infants

Cited by 67 publications

References 13 publications

Role of pH in production of hydrogen from carbohydrates by colonic bacterial flora. Studies in vivo and in vitro.

Role of pH in production of hydrogen from carbohydrates by colonic bacterial flora. Studies in vivo and in vitro.

Similarities and Differences in Gastrointestinal Physiology Between Neonates and Adults: a Physiologically Based Pharmacokinetic Modeling Perspective

Role of Feeding and Vitamin K in Hypoprothrombinemia of the Newborn

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