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The developing gut-lung axis: postnatal growth restriction, intestinal dysbiosis, and pulmonary hypertension in a
Stephen Wedgwood1, Cris Warford1, Sharleen R Agvatisiri1
1Department of Pediatrics, UC Davis School of Medicine, Sacramento, CA, USA.
Insights
Postnatal growth restriction (PNGR) in premature infants causes intestinal dysbiosis and pulmonary hypertension (PH). Probiotic treatment with Lactobacillus reuteri DSM 17938 prevented PH and right ventricular hypertrophy in a rodent model.
Area of Science:
- Neonatal physiology
- Microbiome research
- Pulmonary vascular disease
Background:
- Postnatal growth restriction (PNGR) in premature infants is linked to an increased risk of pulmonary hypertension (PH).
- PNGR exacerbates PH severity when combined with hyperoxia in rodent models.
- This study investigates the hypothesis that PNGR induces intestinal dysbiosis, contributing to PH, and that probiotic intervention can mitigate this effect.
Purpose of the Study:
- To determine if PNGR causes intestinal dysbiosis.
- To investigate if probiotic treatment attenuates PNGR-associated PH.
- To explore the impact of PNGR and hyperoxia on the intestinal microbiota and its relationship with PH.
Main Methods:
- Rodent pups were exposed to room air or hyperoxia, normal or restricted milk intake (PNGR), and probiotic or placebo treatment.
- Pulmonary hypertension (PH) was assessed via echocardiography and right ventricular hypertrophy (RVH) using Fulton's index.
- Intestinal microbiota composition was analyzed using 16S rRNA gene sequencing in the small bowel and cecum.
Main Results:
- PNGR, with or without hyperoxia, significantly altered the intestinal microbiota composition.
- Probiotic treatment with Lactobacillus reuteri DSM 17938 attenuated PH and RVH in PNGR pups but not in those exposed to hyperoxia alone.
- DSM 17938 treatment led to a decrease in intestinal microbial alpha-diversity.
Conclusions:
- PNGR is a cause of intestinal dysbiosis and subsequent PH.
- Lactobacillus reuteri DSM 17938 effectively prevents PNGR-associated RVH and PH.
- Alterations in the developing intestinal microbiota significantly impact lung vasculature and right ventricular development.
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.
