# Lactobacillus rhamnosus GG Alleviates Post-Weaning Stress-Induced Intestinal Barrier Damage and Inflammation by Promoting Intestinal Health and Modulating the Gut Microbiota in Piglets

## TL;DR

This study shows that giving Lactobacillus rhamnosus GG to piglets early in life helps reduce intestinal damage and inflammation after weaning by improving gut health and changing the gut microbiota.

## Contribution

The study provides new insights into how LGG alleviates post-weaning stress in piglets through multi-omics analysis.

## Key findings

- LGG reduced diarrhea and improved intestinal barrier integrity in piglets.
- LGG increased beneficial gut bacteria like Bifidobacterium and Mucispirillum.
- LGG downregulated immune-related pathways, especially the PI3K/AKT pathway.

## Abstract

The aim of this study is to investigate oral administration of L. rhamnosus GG (LGG) in early life on the growth performance, diarrhea, intestinal health, and microbiota of post-weaning piglets. Ninety-six newborn piglets were randomly divided into two groups. Piglets were orally administered with 2 mL of 10% sterile skim milk or 2 mL of 10% sterile skim milk suspended with viable LGG (1 × 108 CFU/mL). Results showed that compared with the control group, oral administration of LGG in early life slightly decreased diarrhea incidence. Furthermore, LGG supplementation maintained the intestinal barrier integrity (HE, DAO) and reduced the generation of the inflammatory response. 16S rRNA sequencing showed that LGG modulated the colon microbiota composition of piglets by increasing the relative abundance of Bifidobacterium, Helicobacter, Mucispirillum, and Dorea. Metabolomic study suggested that LGG substantially influenced the intestinal metabolic profile, particularly compounds associated with the biosynthesis of unsaturated fatty acids. The metabolic alterations were closely linked to the enhancement of the microbial community makeup. The analysis of jejunum RNA sequencing indicated that, in comparison to the CON group, LGG significantly downregulated various immune-related signaling pathways, especially the PI3K/AKT pathways. Correlation analysis of microbiota, metabolism, and genes uncovered a substantial association between the taxa enhanced by LGG and the critical genes in the PI3K/AKT signaling pathways. The coculture system of LGG and intestinal organoids revealed that LGG alleviated TNF-α induced injury through inhibiting the PI3K/AKT signaling pathway. Overall, the integrated analysis of multiple omics approaches revealed that LGG reduced post-weaning induced intestinal injury through the regulation of gut microbiota, modification of metabolic profiles, reinforcement of the intestinal barrier, and downregulation of the PI3K/AKT signaling pathway.