The skin-gut axis theory suggests that the gut and skin barrier, as well as the microbiota, are highly similar and have a bidirectional relationship. Gut good bacteria can reduce the permeability of the gut barrier, alter skin symbiotic bacteria, and enhance skin barrier function, which is beneficial for wound healing. How to improve wound infection and promote healing by improving gut function has become a new research hotspot in recent years.

To compare the effectiveness of two internal nurturing and external treatment for older patients with pressure injury (PI) based on the skin-gut axis theory, and explore new ideas and methods for them.

Considering the skin-gut axis theory and guidelines, we discussed and designed two internal nurturing programs including prebiotics+probiotics or traditional Chinese medicines to regulate gastrointestinal function and replenish nutrients, and the "four-step external treatment", including debridement+negative pressure wound therapy with instillation (NPWTi) +surgical closure+ follow-up with wound care. A two-arms randomized controlled trial (RCT) was adopted and 80 inpatients with fourth stage of PI,≥ 60 years old in department of Medical Aesthetics and Burns, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine were included from August 2023 to July 2025, and were randomly divided into the trial group and the control group according to a 1∶1 ratio. The trial patients were treated by "prebiotics+probiotics" combined with "four-step external treatment". The control patients were treated by "prebiotics+traditional Chinese medicines" combined with "four-step external treatment" until 4 weeks and followed up for 3 months. Primary outcome measures included healing rate and healing time after 4 weeks of intervention and 3-month of follow-up. Secondary outcome measures included serum albumin, hemoglobin, blood glucose levels before and after intervention. Statistical analysis was applied to baseline data, primary and secondary outcomes.

Among the 80 PI patients, there were 54 males (67.5%) and 26 females (32.5%), with an average age of (71.3±11.4) years. The trial group of 40 patients completed treatment and follow-up as planned, with no dropouts or deaths; Two patients in the control group of 40 died. There was no statistically significant difference in baseline data between the two groups of patients (P>0.05). There was no statistically significant difference in the 4-week healing rate and 4-week healing time between the two groups of patients (P>0.05); The 3-month healing rate of the trial group patients was higher than that of the control group (χ² =5.952, P=0.015), and the 3-month healing time was shorter than that of the control group (t=3.440, P=0.001). Three weeks after intervention, there was no statistically significant difference in serum albumin, hemoglobin, and blood glucose levels between the two groups of patients (P>0.05). There was no statistically significant difference in hemoglobin and blood glucose levels between the two groups of patients before and after intervention (P>0.05); After intervention, the serum albumin levels of both groups of patients were higher than before intervention, and the difference was statistically significant (P<0.05).

Both internal nurturing combined with "four-step external treatment" can improve the efficacy of older patients with stage 4 PI, and the trial group showed better results after a 3-month follow-up treatment.