Mediators of Inflammation

Review Article

The Interplay between Immune System and Microbiota in Diabetes

Table 1

Mechanisms of immunomodulation of gut microbiota in diabetes.


Animal model/study group	Main finding	Mechanisms involved	Reference

GF mice Gpr41-/- and +/+	Gpr41 is a regulator of host energy balance through modulation of gut microbiota	Reduced expression of PYY, increased intestinal transit rate, and reduced harvest of energy from the diet	B.S. Samuel et al. [34]
GF mice	Protected against obesity after consuming a Western-style, high-fat, sugar-rich diet	Elevated levels of Fiaf Increased AMPK activity	F. Backhed et al. [35]
GF mice Specific GF mice Bacteroides fragilis gnotobiotic mice	GF mice had a worse exercise performance compared to mice colonized by a single bacterial species and to mice colonized by multiple nonharmful bacteria	Higher serum levels of glutathione peroxidase (GPx) in SPF than GF mice. Lower serum superoxide dismutase activity in BF than SPF and GF mice	Y.J. Hsu et al. [36]
Healthy subjects	Higher fitness level is correlated to gut microbiome diversity	Increased production of butyrate	M. Estaki et al. [38]
T2D subjects	Improved glycemia, functional and anthropometric variables	Reduction of intestinal mycetes overgrowth, gut permeability, and systemic inflammation	E. Pasini et al. [39]
ob/ob mice High-fat diet-fed mice	Chronic antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS	Increased intestinal permeability Reduced expression of genes coding for proteins of tight junctions	P.D. Cani [44]
Mice injected with Streptomyces toxin and bafilomycin A1	Impaired glucose tolerance	Smaller islet pancreatic β-cell mass	M.A. Myers [46]
MyD88-negative mice NOD mice	Colonization of GF mice with intestinal bacteria reduced T1D in MyD88-negative but not in wild-type NOD mice	TLR4-mediated Trif signaling causes a tolerizing immune response	M.P. Burrows [48]
Diabetes-resistant biobreeding rats Diabetes-prone biobreeding (BBDO) rats NOD mice	Bacteria provide protection against diabetes	Transfer of intestinal Lactobacillus johnsonii N 6.2 from diabetes-resistant biobreeding rats to diabetes-prone biobreeding rats. Transmission of segmented filamentous bacteria to NOD mice	K. Lau et al. [51] M.A. Kriegel [52]
NOD mice placed on neutral or acidified water	Acidified water delays T1D onset	Increase in Bacteroidetes, Actinobacteria, and Proteobacteria and decrease in Firmicutes in NOD mice exposed to neutral water. Lower levels of Foxp3 expression in CD4(+)Foxp3(+) cells, decreased CD4(+)IL-17(+) cells, and a lower ratio of IL-17/IFN-γ CD4⁺ T-cells in NOD mice exposed to neutral water.	K.J. Wolf et al.[54]
Obese diabetic mice (wt, p40^-/-and p35^-/-)	Disruption of IL-12 promotes angiogenesis and increases blood flow recovery	Increase in capillary/arteriole density, endothelial nitric oxide synthase/Akt/vascular endothelial growth factor receptor 2 signaling, and a reduction in oxidative stress and inflammation	M. Ali et al. [60]
Nod2^-/- NOD mice Nod2^+/+NOD mice	Nod2^-/- NOD mice are protected from T1D	Colonization of germ-free NOD mice with Nod2^-/-NOD microbiota reduced the number of inflammatory cells and their cytokines, but increased T-regulatory cells	Y. Y. Li et al. [61]
Trained NOD mice Untrained NOD mice	Exercise enhances a beneficial immune-modulation in T1D	Reduced pancreatic infiltrates. Reduced levels of IL-6 and MIP-1β	R. Codella et. al [63]