Role of the Gastrointestinal Tract Microbiome in the Pathophysiology of Diabetes Mellitus

Table 1

Summary of the gut microbiome and metagenomic changes observed in different preclinical and clinical diabetes studies.

Study format	Clinical features/major findings	Microbiome changes	Metagenome/metabolome changes	Reference
Longitudinal infant T1DM	Out of 33 genetically predisposed T1DM infants, 12% developed T1DM, whereas 21% developed T1DM autoantibodies during the first 4 years of life	A decrease in alpha diversity and an overabundance of Blautia and Rikenellaceae	Modulation of sphingomyelin, lithocholic acid, lipids, branch-chained amino acid concentrations, and sugar transport pathways	[55]
Longitudinal infant T1DM	All four enrolled infants developed autoimmunity and T1DM within the first 3 years	Drop in alpha diversity and increase in Bacteroidetes (Bacteroides spp.) and decrease in Firmicutes	Not applicable	[43]
Metagenomics of the microbiome in T1DM patients	Microbial fermentation and functional components promoted autoimmune destruction of beta cells	Higher Bacteroides and lower Prevotella abundance	T1DM patients had higher carbohydrate metabolism, adhesions, motility, phages, prophages, sulfur metabolism, and stress responses	[42]
Metagenomics of the microbiome in T2DM patients microbiome	Not applicable	Microbial dysbiosis characterized by a decrease in butyrate-producing bacteria and an increase in the populations of various opportunistic pathogens	Higher gut oxidative stress and membrane transport of sugars	[46]
Metagenome in T2DM women	Elevated glucose, C peptide, leptin, triglycerides, and oxidative stress	Enriched with Lactobacillus sp. and depletion of Clostridium sp.	Higher sugar metabolism and transport, fatty acid synthesis, and oxidative stress pathways	[58]
Adult T2DM	Ratio of Bacteroidetes to Firmicutes correlated positively and significantly with plasma glucose concentrations	Higher alpha diversity. Changes in beta diversity were characterized by higher Bacteroidetes in T2DM cases and Firmicutes belonging to class Clostridia in controls subjects	Not applicable	[44]
Metagenomics of T2DM patients before and after bariatric surgery	Surgery improved BMI, hypertension, lipid profile, and glycemic index	Bacteroidetes/Firmicutes ratio increased. Several changes in taxonomy composition	Changes in carbohydrate metabolism and the phosphotransferase system	[59]
Antibiotic treatment in high-fat diet-induceddiabetic mice	Antibiotic treatment reduced endotoxemia, glucose intolerance, body weight gain, inflammation, and oxidative stress	Antibiotic treatment changes microbiome architecture of high-fat diet-induced diabetic mice	Drop in endotoxemia, tissue inflammation, and oxidative stress markers	[35]
Fecal transplant from healthy mice to T1DM genetically susceptible mice	Prevents autoimmunity, and insulitis and delays T1DM development	Increase in Bacteroidetes and decrease in Firmicutes and Clostridiaceae and Lactobacillaceae abundance	Increase in IgA, TGFβ concentrations, and CD8+, CD103+, and CD8αβ T cells	[60]
Antibiotic treatment of biobred diabetes-prone rat	Antibiotic treatment delayed/protected against TIDM	Antibiotic treatment lowered Bacteroides spp.	Antibiotic treatment lowered insulitis	[12]