Abstract:
BACKGROUND:Postnatal growth restriction (PNGR) in premature infants increases risk of pulmonary hypertension (PH). In a rodent model, PNGR causes PH, while combining PNGR and hyperoxia increases PH severity. We hypothesized that PNGR causes intestinal dysbiosis and that treatment with a probiotic attenuates PNGR-associated PH. METHOD:Pups were randomized at birth to room air or 75% oxygen (hyperoxia), to normal milk intake (10 pups/dam) or PNGR (17 pups/dam), and to probiotic Lactobacillus reuteri DSM 17938 or phosphate-buffered saline. After 14 days, PH was assessed by echocardiography and right ventricular hypertrophy (RVH) was assessed by Fulton's index (right ventricular weight/left ventricle + septal weight). The small bowel and cecum were analyzed by high-throughput 16S ribosomal RNA gene sequencing. RESULTS:PNGR with or without hyperoxia (but not hyperoxia alone) altered the microbiota of the distal small bowel and cecum. Treatment with DSM 17938 attenuated PH and RVH in pups with PNGR, but not hyperoxia alone. DSM 17938 treatment decreased α-diversity. The intestinal microbiota differed based on oxygen exposure, litter size, and probiotic treatment. CONCLUSION:PNGR causes intestinal dysbiosis and PH. Treatment with DSM 17938 prevents PNGR-associated RVH and PH. Changes in the developing intestine and intestinal microbiota impact the developing lung vasculature and RV.
journal_name
Pediatr Resjournal_title
Pediatric researchauthors
Wedgwood S,Warford C,Agvatisiri SR,Thai PN,Chiamvimonvat N,Kalanetra KM,Lakshminrusimha S,Steinhorn RH,Mills DA,Underwood MAdoi
10.1038/s41390-019-0578-2subject
Has Abstractpub_date
2020-02-01 00:00:00pages
472-479issue
3eissn
0031-3998issn
1530-0447pii
10.1038/s41390-019-0578-2journal_volume
87pub_type
杂志文章abstract::GH insensitivity may be an inherited condition or may arise as a consequence of disease of malnutrition. Laron syndrome is the most severe form of GH insensitivity, arising from an absent or defective GH receptor. Less severe forms of GH insensitivity, however, may exist, resulting in short stature but in few other fe...
journal_title:Pediatric research
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journal_title:Pediatric research
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journal_title:Pediatric research
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journal_title:Pediatric research
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journal_title:Pediatric research
pub_type: 杂志文章
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更新日期:1991-08-01 00:00:00
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journal_title:Pediatric research
pub_type: 杂志文章
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