Multi-omics insights into growth impairment mechanisms in children with persistent diarrhea.
This study highlights the connection between gut microbiota and growth impairment in children with persistent diarrhea, suggesting potential avenues for targeted interventions.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This study investigated mechanisms of short stature in children with persistent diarrhea (PDC) by analyzing gut microbiota and the GH-IGF-1 axis. It compared samples from healthy controls, PDC patients without short stature, and PDC patients with short stature. Findings indicated disruptions in butyrate-producing bacteria and related metabolic pathways in PDC patients with short stature.
Abstract
This study aimed to elucidate the key mechanisms underlying short stature with pediatric persistent diarrhea in children (PDC) and to propose an integrated model linking the butyrate-producing gut microbial niche, short-chain fatty acids (SCFAs), Th17/Treg balance, the growth hormone-insulin-like growth factor 1 (GH-IGF-1) axis, and growth regulation. Samples from healthy controls (HCs), PDC patients without short stature (PDC-NS), and PDC patients with short stature (PDC-S) were analyzed using multi-omics profiling and machine learning-based predictive modeling. The results showed that PDC-S patients exhibited disruption of core butyrate-producing bacterial communities and related metabolic pathways, markedly reduced fecal butyrate levels, systemic Th17/Treg imbalance characterized by a pro-inflammatory state, and dual suppression of receptor- and ligand-level components of the GH-IGF-1 axis. Multi-omics machine learning identified a five-factor risk prediction panel composed of metabolic, immune, and endocrine markers, while causal inference further established butyrate as a central regulator of growth. Mouse experiments further validated that combined intervention with butyrate, Faecalibacterium prausnitzii, and recombinant human growth hormone (rhGH) ameliorated growth retardation. Overall, this study proposes a precision therapeutic strategy based on butyrate and GH co-intervention, providing new mechanistic insights and translational tools for PDC-associated short stature. Importance The research conducted in this study holds significant implications for improving the understanding and treatment of stunted growth with persistent diarrhea in children (PDC). By unraveling the intricate pathways linking gut microbiota, immune responses, and growth hormone regulation, the study sheds light on the underlying mechanisms contributing to stunting in these vulnerable populations. The identification of key factors, such as butyrate-producing bacteria and the Th17/Treg balance, not only enhances our comprehension of PDC-related growth impairment but also offers a promising avenue for targeted interventions. The proposed integrated mechanistic model and intervention strategy pave the way for precision therapies tailored to address the specific biological mechanisms at play, potentially leading to more effective and personalized treatments for children suffering from PDC-associated stunting.
Background
This paper addresses the mechanisms underlying short stature in children with persistent diarrhea, a condition that can significantly impact growth and development. Previous research has suggested a link between gut microbiota and growth regulation, but the specific pathways involved remain poorly understood. This study is significant as it seeks to integrate various biological factors, including gut microbiota, immune responses, and the GH-IGF-1 axis, to provide a comprehensive model of growth impairment in this population.
Methods
The study utilized multi-omics profiling and machine learning-based predictive modeling to analyze samples from healthy controls, PDC patients without short stature, and PDC patients with short stature. The study did not specify the sample size or the duration of the analysis. Primary outcomes included metabolic, immune, and endocrine markers related to growth.
Results
PDC patients with short stature exhibited disruption of core butyrate-producing bacterial communities and related metabolic pathways. The study reported a five-factor risk prediction panel identified through machine learning, although specific numeric findings were not detailed. Causal inference indicated that butyrate plays a central role in growth regulation.
Interpretation
The findings suggest that butyrate and the GH-IGF-1 axis are critical in understanding growth impairment in children with persistent diarrhea. While the statistical significance of the findings is noted, the clinical relevance remains uncertain without specific effect sizes or clinical outcomes reported. The inclusion of mouse experiments raises questions about the applicability of the results to human populations, limiting the conclusions that can be drawn for clinical practice.
Key findings
- PDC-S patients exhibited markedly reduced fecal butyrate levels.
- Systemic Th17/Treg imbalance characterized by a pro-inflammatory state was observed.
- Dual suppression of receptor- and ligand-level components of the GH-IGF-1 axis was noted.
- A five-factor risk prediction panel was identified through multi-omics machine learning.
Limitations
- Mouse experiments may not directly translate to human outcomes.
- Study relies on multi-omics and machine learning, which may complicate interpretation.
- Not reported in abstract.