Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2026 Apr;38(4):337-345. doi: 10.3760/cma.j.cn121430-20250903-00472.
ABSTRACT
OBJECTIVE: To investigate the association between acute kidney injury (AKI) and the gut microbiota by integrating 16S sequencing analysis with mendelian randomization (MR).
METHODS: 1) MR analysis: The genome-wide association study (GWAS) dataset for AKI from the FinnGen consortium and the GWAS dataset for gut microbiota composition from the Dutch Microbiome Project were selected to screen single nucleotide polymorphism (SNP) associated with AKI as instrumental variable (IV) for genetic variation, using AKI as the exposure factor. Potential causal associations between AKI and gut microbiota were analyzed using a two-sample, one-way MR analysis with the primary analysis method of inverse variance weighted (IVW). Heterogeneity analysis was performed using the Cochran Q test. Potential pleiotropy was assessed using the MR-Egger intercept test. Sensitivity analysis was performed using the leave-one-out test. 2) Clinical cohort study: Consecutive patients admitted to the intensive care unit (ICU) of Qingdao Municipal Hospital between December 2024 and March 2025 were prospectively enrolled. Patients were classified into the AKI group or the non-AKI group based on the occurrence of AKI during their ICU stay, according to the diagnostic criteria from Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines (2012). Baseline clinical data were collected within 48 hours of ICU admission, including gender, age, height, weight, body mass index (BMI), major comorbidities, vital signs, serum creatinine (SCr), blood routine, C-reactive protein (CRP), interleukin-6 (IL-6), etc. Anal swabs were collected from patients within 48 hours of ICU admission for 16S rDNA high-throughput sequencing. Significant difference analysis and linear discriminant analysis effect size (LEfSe) were performed to characterize the gut microbiota profile in AKI patients and to further validate the findings from the MR analysis.
RESULTS: 1) MR analysis results: Using the GWAS summary statistics for gut microbiota and AKI, the MR analysis revealed that the genetic liability to AKI was associated with decreased abundance in six gut microbial taxa and increased abundance in one taxon. IVW analysis showed that at the genus level, genetic susceptibility to AKI was associated with lower abundance of Collinsella (β=-0.144, P=0.029), Lachnospiraceaenoname (β=-0.131, P=0.040), Roseburia (β=-0.126, P=0.047), and Parasutterella (β=-0.198, P=0.023). At the species level, AKI genetic susceptibility was linked to reduced abundance of Parasutterellaexcrementihominis (β=-0.197, P=0.024) and Roseburia unclassified (β=-0.280, P=0.012), while being associated with increased abundance of Bacteroidesintestinalis (β=0.358, P=0.013). Cochran Q test showed no heterogeneity, MR-Egger intercept test revealed no pleiotropy, and leave-one-out analysis verified the robustness of the results. 2) Clinical cohort study results: A total of 129 patients were initially enrolled. After excluding 25 patients with incomplete clinical data and 10 whose samples failed to generate sufficient 16S rDNA gene amplification for sequencing, 94 patients were included in the final analysis comprising 72 cases in the AKI group and 22 cases in the non-AKI group. Apart from higher SCr levels in the AKI group than those in the non-AKI group, no statistically significant differences were observed in other baseline clinical characteristics between the two groups. 16S rDNA high-throughput sequencing yielded 6 868 647 high-quality reads, which were clustered into 13 025 amplicon sequence variant (ASV). Significant difference analysis at the species level showed that, compared with the non-AKI group, patients in the AKI group had a relative enrichment of Streptococcus anginosus and Novosphingobium sp. B0.09-8. Conversely, the relative abundances of uncultured Prevotellasp., Alistipesshahii, uncultured Coprococcussp., Collinsellatanakaei, Streptococcus equinus, Alistipesindistinctus, Klebsiellasp. GRB36, and uncultured Oscillospirasp. were significantly lower in the AKI group. LEfSe analysis identified Veillonella unclassified, Ligilactobacillus unclassified, Collinsellatanakaei, Atopobium unclassified, and Streptococcus anginosus as potential biomarkers for the AKI group, whereas Alistipesshahii, uncultured Prevotella sp., and Agathobacter unclassified were more characteristic of the patients in the non-AKI group.
CONCLUSIONS: The MR analysis suggests that the occurrence of AKI exerts an influence on the gut microbiota profile, characterized by a reduction in the abundance of the genus Collinsella. Findings from the real-world study further indicate significant differences in gut microbiota composition between patients with and without AKI. Overall, the gut microbiota of AKI patients is characterized by an enrichment of pro-inflammatory bacteria and a depletion of commensal symbionts. The genus Collinsellamay may serve as a potential biomarker for AKI.
PMID:42200243 | DOI:10.3760/cma.j.cn121430-20250903-00472
