Butyrate-Producing Gut Microbiota Modifies the Association Between Dietary Protein Density and Functional Recovery...

Protein intake may support recovery in older adults, but its functional benefits vary across individuals. We examined whether butyrate-producing gut microbiota modifies the association between dietary protein density and activities of daily living (ADL)-based functional recovery in older patients undergoing post-stroke inpatient rehabilitation.

This registry-based observational study included patients aged ≥65 years admitted to a convalescent rehabilitation hospital after stroke. Dietary intake was assessed from the mean intake during the first week after admission. Gut microbiota was profiled using 16S ribosomal RNA gene sequencing of stool samples collected within 14 days of admission. The primary exposure was dietary protein density, defined as protein intake per 1000 kcal. The effect modifier was a taxonomy-based proportion of taxa annotated as putative butyrate-producing gut bacteria. The primary outcome was Functional Independence Measure motor effectiveness. Multivariable linear regression tested the interaction between standardized dietary protein density and the bacterial proportion.

We analyzed 156 patients (mean age, 78.4 years; 55.8% men); 152 were included in the primary complete-case model. The interaction between dietary protein density and the putative butyrate-producing bacterial proportion was significantly associated with motor ADL recovery (β=0.046, 95% CI 0.013-0.079; p=0.006). The association remained directionally consistent across sensitivity analyses. Similar signals were observed for other FIM-based outcomes, but not for handgrip strength or skeletal muscle mass index.

Butyrate-producing gut microbiota modified the association between dietary protein density and ADL-based functional recovery after stroke. Prospective studies incorporating dietary fiber and direct measures of microbial function and metabolites are needed to establish causality.