Association between Gut Microbiome Dysbiosis and Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes Mellitus: A Multidisciplinary Cross-Sectional Study

Abstract

Background: Diabetic peripheral neuropathy is one of the most frequent chronic complication of type 2 diabetes mellitus and can result in pain, decreased sensation and a diminished quality of life. Recent findings indicate that the gut microbiome changes can play a role in metabolic inflammation, in compromised intestinal barrier function and nerve injury. There is, however, little local evidence to support the association between dysbiosis of the gut microbiota and DPN.

Objective: To determine the association between gut microbiome dysbiosis and diabetic peripheral neuropathy among patients with type 2 diabetes mellitus.

Methods: This multidisciplinary cross-sectional study was conducted at Gomal Medical College, Dera Ismail Khan, from January 2025 to June 2025. Total 76 type 2 diabetes mellitus (T2DM) adult patients were consecutively recruited by non-probability sampling method. Diabetic peripheral neuropathy was evaluated with Michigan Neuropathy Screening Instrument, 10-g monofilament and vibration perception and ankle reflex examination. Bacterial 16S ribosomal RNA gene analysis was performed using fresh stool samples. Alpha diversity was assessed by Shannon, Simpson and Chao1 indices and the composition of bacteria and gut dysbiosis index were compared between patients with and without neuropathy. Multivariable binary logistic regression was employed to determine factors associated with diabetic peripheral neuropathy independently.

Results: Diabetic peripheral neuropathy was identified in 42 of 76 patients, giving a frequency of 55.3%. Patients with neuropathy had a longer duration of diabetes, higher fasting blood glucose, higher HbA1c and increased C-reactive protein levels compared with patients without neuropathy. The Shannon diversity index was significantly lower in the neuropathy group than in the non-neuropathy group (2.71 ± 0.46 versus 3.18 ± 0.51; p<0.001), whereas the gut dysbiosis index was significantly higher (3.8 ± 1.3 versus 2.4 ± 1.0; p<0.001). Patients with neuropathy had reduced abundance of Faecalibacterium, Roseburia, Akkermansia and Bifidobacterium and increased abundance of Escherichia–Shigella and Proteobacteria. The gut dysbiosis index was positively correlated with the neuropathy score (r=0.52; p<0.001). In multivariable analysis, a higher gut dysbiosis index, lower Shannon diversity, longer duration of diabetes and higher HbA1c were independently associated with diabetic peripheral neuropathy.

Conclusion: Gut microbiome dysbiosis was significantly associated with diabetic peripheral neuropathy in patients with type 2 diabetes mellitus. Reduced microbial diversity, depletion of beneficial bacteria and increased abundance of potentially pro-inflammatory microorganisms may contribute to neuropathy through metabolic and inflammatory pathways. Longitudinal studies are needed to determine causality and evaluate microbiome-targeted interventions.