# Sialic acid-responsive Parabacteroides is linked to gut barrier integrity in older adults

## TL;DR

This study shows that a gut bacterium called Parabacteroides helps maintain intestinal barrier integrity in older adults, possibly by using sialic acid from mucin, which could help reduce age-related inflammation.

## Contribution

The study identifies Parabacteroides as a gut microbe linked to intestinal barrier integrity in older adults through its response to sialic acid.

## Key findings

- Parabacteroides is negatively associated with intestinal barrier dysfunction in older adults.
- Parabacteroides growth is promoted by sialic acid and mucin, and it upregulates genes for sialic acid catabolism.
- Fecal sialic acid levels correlate with Parabacteroides abundance, which mediates the link to intestinal barrier markers.

## Abstract

Aging is frequently accompanied by inflammaging—a chronic, low-grade inflammatory state that contributes to functional decline and disease risk. Disruption of the intestinal barrier is increasingly being recognized as a key driver of inflammaging; however, its relationship with the gut microbiota in older adults remains poorly understood. Here, we demonstrate a significant association of intestinal barrier dysfunction markers with systemic inflammatory markers using a cross-sectional study in this population. Notably, the genus Parabacteroides showed a strong negative association with barrier dysfunction. In vitro assays showed that three Parabacteroides lineages predominant in older adults, including P. merdae, enhanced the intestinal barrier integrity in a viability-dependent manner. Fecal sialic acid (Neu5Ac) levels were positively correlated with the abundance of Parabacteroides. Mediation analysis further indicated that Parabacteroides significantly mediated the association between fecal sialic acid and intestinal barrier markers. Culture experiments showed that both sialic acid and mucin, which is rich in terminal sialyl residues, promoted Parabacteroides growth. Transcriptomic analysis of P. merdae cultured with sialic acid revealed upregulation of genes for sialidases, transporters, and enzymes, consistent with sialic acid catabolism and transport, suggesting utilization of mucin-derived sialic acid. Together, these findings indicate that in older adults, Parabacteroides is linked to the intestinal barrier integrity and responds to mucin-associated sialic acid, supporting a model wherein host-derived glycans foster barrier-protective microbes to promote healthy aging. The study findings provide avenues for devising strategies for maintaining the intestinal barrier integrity and reducing age-related inflammation, which may ultimately contribute to the prevention of inflammaging.