Associations of probiotics combined with Tongli Gongxia Chinese medicine with intestinal barrier biomarkers and day 7 short-chain fatty acids in patients with severe acute pancreatitis.

BACKGROUND

Severe acute pancreatitis (SAP) is characterized by intestinal barrier dysfunction and altered short-chain fatty acid (SCFA) profiles, contributing to bacterial translocation and systemic complications. This study examined whether receipt of probiotics combined with Tongli Gongxia Chinese medicine was associated with intestinal barrier biomarker changes and day 7 fecal SCFA concentrations in SAP patients.

METHODS

This single-center retrospective cohort study included 240 SAP patients hospitalized between January 2019 and December 2024. After 1:1 propensity score matching, 200 patients (100 per group) were analyzed. The combination therapy group received multi-strain probiotics and Tongli Gongxia formula (Dachengqi Decoction) initiated within 72 hours of admission, plus standard therapy. The control group was restricted to patients receiving standard therapy alone during the corresponding early-treatment window. Primary outcomes were changes in four serum intestinal barrier biomarkers (diamine oxidase [DAO], D-lactate, lipopolysaccharide [LPS], and intestinal fatty acid-binding protein [I-FABP]) from baseline to day 7. Secondary outcomes included day 7 fecal SCFA concentrations, clinical outcomes, and safety events. Because baseline fecal SCFA samples were not available, SCFA analyses were interpreted as cross-sectional day 7 comparisons rather than treatment-induced changes.

RESULTS

Combination therapy was associated with greater reductions in barrier dysfunction biomarkers: ΔDAO -2.6 U/L (95% CI -3.8 to -1.4, p<0.001), ΔD-lactate -1.3 mmol/L (95% CI -1.9 to -0.7, p<0.001), ΔLPS -0.09 EU/mL (95% CI -0.13 to -0.05, p<0.001), and ΔI-FABP -216 pg/mL (95% CI -328 to -104, p<0.001). Day 7 SCFA concentrations were higher in the combination therapy group: total SCFAs 105.6 vs 85.0 μmol/g (p=0.001), including butyrate 14.6 vs 10.8 μmol/g (p=0.003). ICU stay was shorter by 2 days (11 vs 13 days, p=0.03). No probiotic-associated infections occurred. Diarrhea rates were similar (28% vs 18%, p=0.09).

Conclusions

In this retrospective matched cohort, probiotics combined with Tongli Gongxia Chinese medicine were associated with greater improvement in intestinal barrier biomarkers, higher day 7 fecal SCFA concentrations, shorter ICU stay, and acceptable safety. These hypothesis-generating findings merit investigation in randomized trials.