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

Intestinal barrier dysfunction markers were significantly associated with systemic inflammatory markers in older adults.

• Cross-sectional study design was used in an older adult population.
• Intestinal barrier dysfunction markers and systemic inflammatory markers showed significant positive associations.
• This association supports the concept of inflammaging — chronic, low-grade inflammation contributing to functional decline and disease risk — being driven in part by intestinal barrier disruption.

The genus Parabacteroides showed a strong negative association with intestinal barrier dysfunction markers in older adults.

• The association was identified through cross-sectional analysis of the older adult cohort.
• Parabacteroides abundance was inversely related to markers indicative of impaired gut barrier integrity.
• This finding was among the notable microbiota-barrier relationships identified in the study.

Three Parabacteroides lineages predominant in older adults, including P. merdae, enhanced intestinal barrier integrity in vitro in a viability-dependent manner.

• In vitro assays were used to assess the effect of Parabacteroides on intestinal barrier integrity.
• The barrier-enhancing effect was viability-dependent, indicating a requirement for live bacteria.
• The three Parabacteroides lineages tested were those found to be predominant in the older adult population studied.

Fecal sialic acid (Neu5Ac) levels were positively correlated with the abundance of Parabacteroides in older adults.

• Fecal sialic acid was measured as Neu5Ac in stool samples from the study cohort.
• A positive correlation was observed between fecal Neu5Ac levels and Parabacteroides abundance.
• This correlation suggested a potential substrate-microbe relationship in the gut.

Mediation analysis indicated that Parabacteroides significantly mediated the association between fecal sialic acid and intestinal barrier markers.

• Formal mediation analysis was conducted to assess the role of Parabacteroides in the sialic acid–barrier integrity relationship.
• Parabacteroides was identified as a significant mediator between fecal sialic acid levels and intestinal barrier dysfunction markers.
• This finding supports a mechanistic pathway wherein sialic acid promotes Parabacteroides growth, which in turn supports barrier integrity.

Both sialic acid and mucin, which is rich in terminal sialyl residues, promoted Parabacteroides growth in culture experiments.

• Culture experiments were performed supplementing growth media with sialic acid (Neu5Ac) and mucin.
• Mucin was noted to be rich in terminal sialyl residues, providing a substrate for sialic acid release.
• Growth promotion by both substrates supports the ability of Parabacteroides to utilize mucin-derived sialic acid.

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.

• RNA-based transcriptomic analysis was performed on P. merdae grown in the presence of sialic acid.
• Upregulated genes included those encoding sialidases, sialic acid transporters, and catabolic enzymes.
• The gene expression pattern was described as 'consistent with sialic acid catabolism and transport,' suggesting active utilization of mucin-derived sialic acid.
• These findings provide molecular evidence for the mechanism by which Parabacteroides responds to mucin-associated sialic acid in the gut environment.