# Intestinal Microbiota Mediates the Beneficial Effects of γ-Polyglutamic Acid on Calcium Homeostasis and Bone Properties in Lambs

## TL;DR

This study shows that γ-PGA improves calcium absorption and bone health in lambs by enhancing gut health and modulating gut microbes.

## Contribution

The novel finding is that γ-PGA's benefits on calcium and bone health are mediated by specific gut microbes and intestinal transporters.

## Key findings

- γ-PGA at 1.2 g/(d·head) improved lamb growth and duodenal health.
- γ-PGA increased expression of calcium transporters and altered calcium-regulating hormones.
- γ-PGA reshaped the duodenal microbiota, identifying key microbial hubs like [Eubacterium]_ruminantium_group.

## Abstract

Optimizing calcium metabolism is crucial for skeletal development and overall productivity in growing ruminants. Twenty-four Sunite lambs were randomly assigned to four groups and fed 0, 0.6, 1.2, or 2.4 g/(d·head) of γ-PGA for 60 days. Growth performance, serum parameters, duodenal morphology and calcium transporter expression, bone microarchitecture, and duodenal microbiota were analyzed. Supplementation with 1.2 g/(d·head) of γ-PGA (the M group) yielded optimal results, significantly improving final body weight and size. It enhanced duodenal health, evidenced by increased villus height, crypt depth, and microvilli density. Crucially, this dose significantly upregulated the expression of key duodenal calcium transporters (TRPV5/6, CaBPD9k, PMCA, VDR, claudin-12) and altered systemic calcium-regulating hormones (elevated calcitriol, PTH, FGF23). Bone micro-CT analysis revealed changes in trabecular architecture indicative of active remodeling. 16S rRNA sequencing and weighted OTU co-expression network analysis (WOCNA) revealed that γ-PGA reshaped the duodenal microbiota and identified core microbial modules strongly associated with host phenotypes. Genera such as [Eubacterium]_ruminantium_group, Fusicatenibacter, and Prevotella emerged as central hubs. In conclusion, dietary γ-PGA at 1.2 g/(d·head) enhances calcium absorption and bone metabolism in lambs through a coordinated modulation of intestinal integrity and calcium transport, systemic endocrine responses, and the duodenal microbial community, with specific microbiota identified as potential key mediators associated with these effects.