腸内細菌叢と褥瘡の因果関係：2サンプルの双方向メンデルランダム化研究

Pressure ulcers (PUs) remain a major clinical challenge, particularly among immobilized and critically ill patients. Accumulating evidence suggests that alterations in gut microbiota composition and diversity are associated with PUs. But until now, the causal association between them has been unclear.

We conducted a two-sample Mendelian randomisation (MR) study to investigate the causal effect of gut microbiota on PUs.

Gut microbiota summary statistics were obtained from the MiBioGen Consortium (18,340 individuals, 24 cohorts, 211 taxa), and PU data were derived from the FinnGen biobank (354,567 Europeans; 1479 PU cases, 353,088 controls). Causal estimates were calculated using inverse variance weighted (IVW), weighted median, simple mode, weighted mode and MR-Egger methods, with sensitivity analyses including pleiotropy tests, Cochran's Q and leave-one-out analysis. MR Steiger's test was applied to infer directionality.

IVW analysis indicated protective effects of Clostridiaceae 1 (odds ratio, OR = 0.668, 95% confidence intervals (CI) = 0.455-0.982, p = 0.040), genus Coprococcus2 (OR = 0.508, 95% CI = 0.344-0.751, p = 0.001) and genus Gordonibacter (OR = 0.812, 95% CI = 0.676-0.976, p = 0.027) against PUs. While genus Anaerotruncus (OR = 1.729, 95% CI = 1.189-2.513, p = 0.004) and genus Christensenellaceae R7 (OR = 1.953, 95% CI = 1.087-3.508, p = 0.025) increased PUs' risk. Reverse MR suggested causal effects of PUs on five genera, including Butyrivibrio (OR = 0.887, 95% CI = 0.798-0.985, p = 0.026), Erysipelotrichaceae UCG003 (OR = 1.057, 95% CI = 1.004-1.113, p = 0.035), Eubacterium fissicatena group (OR = 0.898, 95% CI = 0.811-0.995, p = 0.040), Faecalibacterium (OR = 0.952, 95% CI = 0.908-0.999, p = 0.046) and Eubacterium oxidoreducens group (OR = 1.093, 95% CI = 1.001-1.194, p = 0.047). Sensitivity analysis supported the robustness of the findings, and Steiger's test confirmed directionality from gut microbiota to PUs.

This MR study provides genetic evidence for a causal role of gut microbiota in PU risk, supporting the potential of microbiota-targeted interventions and offering new insights into PU pathogenesis and highlighting their particular relevance for prevention strategies in immobilized critical care patients.

The study provides epidemiological evidence for a gut-skin link in PUs and suggests personalised microbiota-based intervention strategies for critically bedridden patients.