Stunting is associated with persistent and transferable alterations in the gut microbiome

Area of Science:

• Microbiome research
• Pediatric nutrition
• Gastroenterology

Background:

• Childhood stunting is a major global health issue with poorly understood pathophysiology.
• Robust animal models for studying stunting are lacking.
• Gut microbiota alterations are implicated in stunting.

Purpose of the Study:

• To comparatively characterize the gut microbiota of stunted vs. healthy Kenyan toddlers.
• To establish a gnotobiotic (Gn) pig fecal transplant model to study stunting-associated microbial communities.
• To understand the functional and compositional differences in the gut microbiome related to stunting.

Main Methods:

• Comparative analysis of gut microbiota in Kenyan toddlers (12-24 months) stratified by nutritional status (stunted vs. healthy).
• Fecal microbiota transplantation into gnotobiotic pigs to create a model system.
• Bacterial composition analysis, virulence gene profiling, antimicrobial resistance (AMR) gene detection, and functional pathway analysis (e.g., CAZymes).

Main Results:

• Distinct bacterial compositions were observed: Proteobacteria dominated in stunted toddlers, while Actinobacteria were prevalent in healthy toddlers.
• While diversity indices were similar, unique bacterial genera were identified in each group.
• Stunted toddlers' microbiota showed more AMR genes, whereas healthy toddlers had more virulence genes, suggesting better pathogen control.
• Functional analysis revealed enriched carbohydrate biosynthesis and catabolic pathways in stunted toddlers, and carbohydrate degradation and anabolic pathways in healthy toddlers.
• These microbial patterns and functional differences were successfully recapitulated in the gnotobiotic pig model.

Conclusions:

• The gnotobiotic pig model effectively mimics human infant gut microbial communities and the impact of stunting.
• Distinct gut microbiota compositions and functions are associated with childhood stunting.
• This study provides a valuable model and insights for developing targeted interventions for malnourished and stunted populations.
• Findings support advancing microbiome-based diagnosis and personalized medicine for stunting.