Microbiota-derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo.

BACKGROUND: The diet and microbiome contribute to metabolic disease in part due to increased intestinal inflammation and permeability. Dietary tryptophan is metabolized by both mammalian and bacterial enzymes. Using in vitro, in vivo models, and clinical data, we tested whether bacterial tryptophan indole derivatives underlie the positive benefits of microbiota on inflammation that is associated with metabolic disease. METHODS: In high-fat diet (HFD)-fed mice intestinal permeability and plasma endotoxin levels were measured after indole-3-propionic acid (IPA; 20 mg kg-1 p.o. for 4 days). Tryptophan derivatives effect on permeability and gene expression were assessed in T84 intestinal cell monolayers, in the presence or absence of pro-inflammatory cytokines. Plasma tryptophan metabolites were analyzed from lean, or obese T2D subjects undergoing Roux-en-Y gastric bypass surgery (RYGB). KEY RESULTS: IPA reduced the increased intestinal permeability observed in HFD-fed mice. Of 16 metabolites tested in vitro, only IPA, and tryptamine reduced T84 cell monolayer permeability compromised by pro-inflammatory cytokines. In T84 cells, IPA reversed the IFN-γ induced increase of fructose transporter SLC2A5 (GLUT5) mRNA, but not induction of inflammatory or metabolic genes. In obese subjects, IPA levels were reduced relative to lean counterparts, and these levels were increased by 3 months after RYGB. CONCLUSIONS AND INFERENCES: The novel findings are that obese subjects have lower levels of IPA, a solely bacterially derived tryptophan derivative, and IPA improved intestinal barrier function in vitro and DIO mice. Reduced plasma IPA levels and reversal by surgery may be a consequence of intestinal indole-producing microbiota but underlying mechanisms warrant further investigation.

Pulse oximetry: an alternative method for the assessment of oxygenation in newborn infants.

Continuous monitoring of oxygenation in sick newborns is vitally important. However, transcutaneous PO2 measurements have a number of limitations. Therefore, we report the use of the pulse oximeter for arterial oxygen saturation (SaO2) determination in 26 infants (birth weights 725 to 4,000 g, gestational ages 24 to 40 weeks, and postnatal ages one to 49 days). Fetal hemoglobin determinations were made on all infants and were repeated following transfusion. SaO2 readings from the pulse oximeter were compared with the SaO2 measured in vitro on simultaneously obtained arterial blood samples. The linear regression equation for 177 paired measurements was: y = 0.7x + 27.2; r = .9. However, the differences between measured SaO2 and the pulse oximeter SaO2 were significantly greater in samples with greater than 50% fetal hemoglobin when compared with samples with less than 25% fetal hemoglobin (P less than .001). The pulse oximeter was easy to use, recorded trends in oxygenation instantaneously, and was not associated with skin injury. We conclude that pulse oximetry is a reliable technique for the continuous, noninvasive monitoring of oxygenation in newborn infants.

Pulse oximetry--an alternative to transcutaneous PO2 in sick newborns.

In summary, the pulse oximeter provides a reliable, continuous assessment of oxygenation in newborn infants. Its rapid response time and ease of use make it a practical device for use on all sick newborns. To avoid hyperoxia it should be used in conjunction with arterial blood gas measurements and we recommend a high SaO2 alarm of 92% in infants with predominantly fetal hemoglobin. Finally, it is an improved way of monitoring oxygenation in very immature infants and in infants with bronchopulmonary dysplasia.