Impact of type 1 diabetes on the composition and functional potential of gut microbiome in children and adolescents: possible mechanisms, current knowledge, and challenges

Abstract

Diabetes prevalence and incidence among youth have been increasing globally. Type 1 Diabetes (T1D) in children or adolescents accounts for 5-10% of all diagnosed cases of diabetes. Emerging evidence indicates that genetic factors, especially genes in the human leukocyte antigen region, are not the only factors involved in the predisposition of an individual to T1D. The pathogenesis and development of T1D is driven by both genetic predisposition and environmental factors. Studies indicate that gut microbiota is one of the potential environmental influencers involved in the pathophysiology of TID. Gut microbiota mediates the development of diabetes by altering intestinal permeability, modifying intestinal immunity, and molecular mimicry. The gut microbial diversity, taxonomic profile, and functional potential of gut microbes are significantly altered in individuals with T1D as compared to healthy individuals. However, studies are still needed to identify the specific microbes and microbial metabolites that are involved in the development and pathogenesis of T1D. This will help the development of microbiome-based therapeutic strategies for the prevention and treatment of T1D. The present review article highlights the following: (i) the current knowledge and knowledge gaps in understanding the association between T1D and gut microbiome specifically focusing on the composition and functional potential of gut microbiome in children and adolescents, (ii) the possible mechanisms involved in gut microbiome-mediated T1D pathogenesis, and (iii) challenges and future direction in this field.

Islet autoantibody seroconversion in type-1 diabetes is associated with metagenome-assembled genomes in infant gut microbiomes

“…Positive IA-association was found with 312 out of 327 MAGs in Bacteroides uniformis , 41 out of 43 MAGs in Bacteroides cellulosilyticus , all 11 MAGs in Bacteroides intestinalis , 31 out of 44 MAGs in Bacteroides stercoris and 18 out of 170 MAGs in Bacteroides ovatus . Elevated abundances of the Bacteroides genus, including Bacteroides uniformis and Bacteroides ovatus at the species level, have been reported in seroconverted and T1D subjects 8 , 27 , 28 Findings of elevated abundance of Bacteroides cellulosilyticus , Bacteroides intestinalis and Bacteroides stercoris have been reported in T1D patients 29 Our analysis of MAGs confirmed the positive and consistent signal of IA-association with Bacteroides uniformis, Bacteroides cellulosilyticus , Bacteroides intestinalis , Bacteroides stercoris , and Bacteroides ovatus .…”

Lactobacillus murinus alleviate intestinal ischemia/reperfusion injury through promoting the release of interleukin-10 from M2 macrophages via Toll-like receptor 2 signaling

“…The human gastrointestinal tract houses a vast and diverse intestinal microflora that provides nutrients and intrinsic immunity, regulates epithelial cell growth, and fundamentally affects human health and disease [5]. We have previously confirmed that intestinal I/R induces significant intestinal flora disorders and indicated that intestinal microbial metabolites play an important regulatory role in intestinal I/R injury [6].…”

The role of intestinal microbiota and its metabolites in intestinal and extraintestinal organ injury induced by intestinal ischemia reperfusion injury

“…There are direct or indirect interactions between them, and they form a complex interaction network with the host through direct contact, secreting proteins or metabolites, forming a dynamically balanced micro-ecosystem, which is closely related to human health and disease [26][27][28][29]. Existing studies have shown that intestinal microbiota is closely related to the occurrence and development of diabetes, hypertension, cardiovascular disease, tumors, etc., because of its important role in human health, it is also called the human body's forgotten organs [9,[30][31][32][33][34][35][36]. In addition, the intestinal microbiota is huge, and it contains about 100 times the number of genes in the human genome, so it is also known as the second genome of the human body [17,37,38].…”