The diversity and abundance of gut microbiota are associated with the pain sensation threshold in the Japanese population

Abstract

Small fibre neuropathy (SFN) is an initial pathology of diabetic polyneuropathy (DPN). Serum lipopolysaccharide binding protein levels are positively correlated with the pain threshold in the foot, suggesting that the abundance of gut Gram-negative bacilli, which are a source of lipopolysaccharides, may be involved in the development of DPN. Furthermore, the abundance of the gut and oral microbiota is assumed to be involved in the pathogenesis of diabetes. Nevertheless, the association between SFN and the microbiota has not been clarified. A total of 1056 individuals were recruited in the 2018 Iwaki Health Promotion Project. Pain sensation was evaluated based on the pain threshold from intraepidermal electrical stimulation (PINT). Patients with PINT scores <0.15 mA were categorized into the low-PINT group (n = 718); otherwise, they were categorized into the high-PINT group (n = 283). Furthermore, each group was divided into the subjects with or without glucose tolerance based on HbA1c levels, fasting blood glucose levels and diabetic history. Principal coordinate analysis and α- and β-diversity of the microbiota were evaluated. The correlation between clinical and microbiota data was examined. Oral microbiota diversity showed no structural differences according to PINT scores, whereas principal coordinate analysis and α- and β-diversity revealed significant structural differences in gut microbiota (p < 0.01, p < 0.05 and p < 0.05, respectively), even after the participants with glucose intolerance were excluded (p < 0.01, p < 0.05 and p < 0.05, respectively). The relative abundance of the genus Bacteroides was significantly lower in high-PINT participants compared with low-PINT participants (10 ± 6.7% vs. 11.3 ± 7.0%, p < 0.01), even after the exclusion of subjects with diabetes and impaired fasting glucose (10.0 ± 6.5% vs. 11.2 ± 6.9%, p < 0.05). In univariate linear regression analyses, PINT was significantly correlated with metabolic syndrome parameters, eGFR, uric acid level and the abundance of Bacteroides. The correlation between Bacteroides and PINT scores remained significant after adjustment for multiple factors (β = -0.07181, p < 0.05). Changes of bacterial diversity and a low abundance of gut Bacteroides were correlated with elevated PINT scores in the Japanese population. This correlation may represent a new therapeutic option for SFN.

Keywords: Diabetic polyneuropathy; Gut microbiota; Oral microbiota; Pain threshold from intraepidermal electrical stimulation; Small fibre neuropathy.