Unveiling the gut connection: Exploring the link between microbiota and type 1 diabetes onset in pediatric patients

Abstract

With the increasing occurrence of type 1 diabetes mellitus (T1DM) in younger individuals, it is important to identifying contributing factors. A retrospective case control pilot study involving 31 children within the first 6 months after diagnosis, was conducted in the Elias Hospital in Bucharest, Romania) between January 2019- December 2021. Spearman correlation analysis was performed, evaluating the association between microbiota and early onset T1DM, high-level onset glycaemia, ketoacidosis, thyroid autoimmunity and clinical parameters involving growth. Gut dysbiosis with an overabundance of bacteria and fungi was observed compared with the healthy control group. Butyricicoccus was positively associated with younger age at onset (r=0.6276, P=0.0018) but negatively correlated with markers of disease progression, such as T1DM recent diagnosis (r=-0.517, P=0.0164), homeostasis model assessment of β-cell function) (r=-0.5962, P=0.0034) and C-peptide values (r=-0.5005, P=0.0344). Bacteroides showed a negative association with early-stage diabetes (r=-0.4431, P=0.0442) and Clostridium leptum was negatively associated with recent diagnosis (r=-0.6278, P=0.0023). Antibiotic use prior to disease diagnosis was positively correlated with Candida albicans (r=0.4431, P=0.0442). Inflammation, determined by the systemic inflammatory index, was positively correlated with Enterobacteriaceae (r=0.4331, P=0.0441) and negatively correlated with Clostridium coccoides (r=-0.4241, P=0.0492). C-reactive protein levels were negatively associated with Bacteroides (r=-0.4331, P=0.0498). These findings highlighted the role of gut microbiota in pancreatic inflammation and T1DM progression. In conclusion, dysbiosis of children with T1DM was correlated with younger age and a more severe onset. Microbial metabolites levels differed in these patients compared with the healthy control group. To the best of our knowledge, the present study is the first to assess gastrointestinal dysbiosis in T1DM.

Keywords: dysbiosis; microbiota; pediatric patient; type 1 diabetes.

Figure 1

Beneficial bacteria abundance in T1DM. Relative abundance of (A) Bifidobacterium, (B) Lactobacillus and (C) A. muciniphila in patients with T1DM compared with healthy control group. ^***P<0.001. T1DM, type 1 diabetes mellitus.

Figure 2

Mycobiome characterization. Dysbiosis with increased abundance of (A) Aspergillus (B) Candida spp. and (C) Saccharomyces in T1DM. The primers were specific to the ribosomal 18S RNA gene and designed tEo recognize various Candida and Saccharomyces spp. T1DM, type 1 diabetes mellitus. ^*P<0.05.

Figure 3

Dysbiosis markers in T1DM. Dysbiosis with increased abundance of (A) Clostridium coccoides and (B) Bacteroides spp. in T1DM. (C) Dysbiosis with increased abundance of Enterobacteriaceae in T1DM (P=0.0193). T1DM, type 1 diabetes mellitus. ^*P<0.05 and ^**P<0.01

Figure 4

Abundance of butyrate-producing bacteria (A) Relative abundance of Clostridium leptum. (B) Dysbiosis with a decrease of Butyricicoccus spp. in T1DM group. T1DM, type 1 diabetes mellitus. ^*P<0.05.

Figure 5

Spearman correlation coefficients between clinical parameters (and relative abundance of bacterial taxa in the microbiome. Red, positive correlation; blue, negative correlations; intensity of color corresponds to the magnitude of the correlation. HbA1C, Hemoglobin A1c (glycated hemoglobin); HOMA-B, Homeostatic Model Assessment of β-cell function; IGF, Insulin-like Growth Factor; CRP, C-reactive Protein; TTG Ab, Tissue Transglutaminase Antibodies; fT4, Free Thyroxine; TSH, Thyroid-Stimulating Hormone; PTH, Parathyroid Hormone.

Figure 6

Fecal metabolite analysis in patients with T1DM and healthy controls. In fecal samples, acetate represented the predominant SCFA, accounting for ~85% in controls and ~92% in T1DM patients. Lactate and butyrate contributed ~10 and ~5% in controls, compared with ~6 and ~2% in T1DM patients, respectively. T1DM, type 1 diabetes mellitus.